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Gusti Y, Liu W, Athar F, Cahill PA, Redmond EM. Endothelial Homeostasis Under the Influence of Alcohol-Relevance to Atherosclerotic Cardiovascular Disease. Nutrients 2025; 17:802. [PMID: 40077672 PMCID: PMC11901717 DOI: 10.3390/nu17050802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 02/21/2025] [Accepted: 02/23/2025] [Indexed: 03/14/2025] Open
Abstract
Alcohol, in the form of ethyl alcohol or ethanol, is a widely consumed substance with significant implications for human health. Research studies indicate multifaceted effects of alcohol on the cardiovascular system with both protective and harmful effects on atherosclerotic cardiovascular disease (ASCVD), depending on the amount involved and the pattern of consumption. Among the critical components of the cardiovascular system are endothelial cells which line blood vessels. These cells are pivotal in maintaining vessel homeostasis, regulating blood flow, and preventing thrombosis. Their compromised function correlates with arterial disease progression and is predictive of cardiovascular events. Here we review research investigating how alcohol exposure affects the endothelium to gain insight into potential mechanisms mediating alcohol's influence on ASCVD underlying heart attacks and strokes. Studies highlight opposite effects of low versus high levels of alcohol on many endothelial functions. In general, low-to-moderate levels of alcohol (~5-25 mM) maintain the endothelium in a non-activated state supporting vascular homeostasis, while higher alcohol levels (≥50 mM) lead to endothelial dysfunction and promotes atherosclerosis. These biphasic endothelial effects of alcohol might underlie the varying impacts of different alcohol consumption patterns on ASCVD.
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Affiliation(s)
| | | | | | | | - Eileen M. Redmond
- Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642-8410, USA; (Y.G.); (W.L.); (F.A.); (P.A.C.)
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2
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Padovan JC, Dourado TMH, Pimenta GF, Bruder-Nascimento T, Tirapelli CR. Reactive Oxygen Species Are Central Mediators of Vascular Dysfunction and Hypertension Induced by Ethanol Consumption. Antioxidants (Basel) 2023; 12:1813. [PMID: 37891892 PMCID: PMC10604002 DOI: 10.3390/antiox12101813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/23/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023] Open
Abstract
Consumption of high amounts of ethanol is a risk factor for development of cardiovascular diseases such as arterial hypertension. The hypertensive state induced by ethanol is a complex multi-factorial event, and oxidative stress is a pathophysiological hallmark of vascular dysfunction associated with ethanol consumption. Increasing levels of reactive oxygen species (ROS) in the vasculature trigger important processes underlying vascular injury, including accumulation of intracellular Ca2+ ions, reduced bioavailability of nitric oxide (NO), activation of mitogen-activated protein kinases (MAPKs), endothelial dysfunction, and loss of the anticontractile effect of perivascular adipose tissue (PVAT). The enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a central role in vascular ROS generation in response to ethanol. Activation of the renin-angiotensin-aldosterone system (RAAS) is an upstream mechanism which contributes to NADPH oxidase stimulation, overproduction of ROS, and vascular dysfunction. This review discusses the mechanisms of vascular dysfunction induced by ethanol, detailing the contribution of ROS to these processes. Data examining the association between neuroendocrine changes and vascular oxidative stress induced by ethanol are also reviewed and discussed. These issues are of paramount interest to public health as ethanol contributes to blood pressure elevation in the general population, and it is linked to cardiovascular conditions and diseases.
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Affiliation(s)
- Júlio C. Padovan
- Laboratory of Blood and Vascular Biology, The Rockefeller University, New York, NY 10065, USA;
| | - Thales M. H. Dourado
- Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto 14040-902, SP, Brazil; (T.M.H.D.); (G.F.P.)
- Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-902, SP, Brazil
| | - Gustavo F. Pimenta
- Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto 14040-902, SP, Brazil; (T.M.H.D.); (G.F.P.)
- Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-902, SP, Brazil
| | - Thiago Bruder-Nascimento
- Department of Pediatrics and Vascular Medicine Institute (VMI), University of Pittsburgh, Pittsburgh, PA 15260, USA;
| | - Carlos R. Tirapelli
- Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-902, SP, Brazil
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Hwang CL, Muchira J, Hibner BA, Phillips SA, Piano MR. Alcohol Consumption: A New Risk Factor for Arterial Stiffness? Cardiovasc Toxicol 2022; 22:236-245. [PMID: 35195845 PMCID: PMC8863568 DOI: 10.1007/s12012-022-09728-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 02/04/2022] [Indexed: 02/06/2023]
Abstract
The relationship between alcohol consumption and cardiovascular disease risk is complex. Low-to-moderate daily alcohol consumption (1–2 drinks/day) is associated with reduced risk, whereas greater amounts of alcohol consumption and a “binge” pattern of drinking are associated with increased cardiovascular risk and mortality. Arterial stiffness may help explain the complex relationship. This integrated review summarizes data from studies examining the associations between alcohol consumption and pulse wave velocity, a gold standard measure of arterial stiffness. We also briefly review the concept and methodology of pulse wave velocity measurement as well as the mechanisms of alcohol-induced arterial stiffening. Findings among the different studies reviewed were inconsistent with methodological challenges related to alcohol use assessment. While making specific conclusions regarding this relationship is tenuous; the data suggest that excessive alcohol consumption or a binge drinking pattern is associated with increased arterial stiffness.
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Affiliation(s)
- Chueh-Lung Hwang
- Department of Physical Therapy, University of Illinois at Chicago, Chicago, USA
| | - James Muchira
- School of Nursing, Vanderbilt University, 461 21st Avenue South, 415 Godchaux Hall, Nashville, TN, 37240-1119, USA
| | - Brooks A Hibner
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, USA
| | - Shane A Phillips
- Department of Physical Therapy, University of Illinois at Chicago, Chicago, USA
| | - Mariann R Piano
- School of Nursing, Vanderbilt University, 461 21st Avenue South, 415 Godchaux Hall, Nashville, TN, 37240-1119, USA.
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Olatoye FJ, Akindele AJ, Onwe S. Ameliorative effect of Kolaviron, an extract of Garcinia kola seeds, on induced hypertension. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2021; 19:37-46. [PMID: 33977689 DOI: 10.1515/jcim-2020-0354] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 01/08/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Early diagnosis and management of known cardiovascular disease risk attributes such as hypertension lessens morbidity and mortality as well as increase quality of life of patients. This present study was modelled to investigate the ameliorative effect of Kolaviron, an extract of Garcinia kola Heckel seeds, in ethanol- and sucrose-induced hypertension. METHODS Test animals were divided into six groups of six animals each for each hypertensive model. Animals were treated daily with distilled water (10 ml/kg); 35% ethanol (3 g/kg) or sucrose (5-7%); Kolaviron (50, 100 and 200 mg/kg) separately plus ethanol or sucrose and Amlodipine (0.14 mg/kg) separately plus ethanol or sucrose for 8 weeks. Systolic, diastolic and mean arterial pressures were determined using non-invasive BP system after 8 weeks. Blood was obtained for the assessment of biochemical parameters, lipid profile and antioxidant indices. Vital organs were collected for approximation of tissue antioxidant levels. RESULTS Results show that Kolaviron at various doses and Amlodipine significantly reduced (p<0.05-0.001) the elevated systolic, diastolic, and mean arterial pressures produced by ethanol and sucrose administration. Additionally, Kolaviron and Amlodipine significantly overturned (p<0.05-0.001) the reduction in GSH, SOD and CAT, and elevation in MDA levels elicited by ethanol and sucrose. Furthermore, Kolaviron and Amlodipine produced significant reduction (p<0.001) in levels of cholesterol, triglycerides and low-density lipoproteins, as well as significant increase (p<0.01-0.001) in levels of high-density lipoproteins. CONCLUSIONS Results from this study demonstrate that Kolaviron possibly possesses significant antihypertensive effect which may possibly be attributed to its antioxidant effects and relative improvement of lipid profile.
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Affiliation(s)
- Francis J Olatoye
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Abidemi J Akindele
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Samson Onwe
- Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
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Hypotensive and Antihypertensive Properties and Safety for Use of Annona muricata and Persea americana and Their Combination Products. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2020:8833828. [PMID: 33488751 PMCID: PMC7787783 DOI: 10.1155/2020/8833828] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 10/22/2020] [Accepted: 11/23/2020] [Indexed: 11/17/2022]
Abstract
Introduction In the management of hypertension (a cardiovascular disease and the leading metabolic risk factor in noncommunicable diseases) with herbal medicines, efficacy and safety are of uttermost concern. This study sought to establish hypotensive, antihypertensive, drug interaction, and safety for use of the aqueous leaf extracts of Annona muricata (AME), Persea americana (PAE), or their combination products (CAPE). Methodology. Systolic and diastolic blood pressure (SBP and DBP), mean arterial blood pressure (MAP), and heart rate (HR) were measured in normotensive Sprague-Dawley rats treated with 50-150 mg/kg of AME, PAE, or CAPE to establish a hypotensive effect. "Combination index" was calculated to establish interaction between AME and PAE. The antihypertensive effect of CAPE was established by measuring SBP, DBP, MAP, and HR in ethanol-sucrose- and epinephrine-induced hypertension. Full blood count, liver and kidney function tests, and urinalysis were determined in ethanol/sucrose-induced hypertension to establish safety for use. Results AME, PAE, and CAPE significantly (p ≤ 0.001) decreased BP in both normotensive and hypertensive animals. Effects of CAPE 1, CAPE 2, and CAPE 3 were synergistic (combination indices of 0.65 ± 0.07, 0.76 ± 0.09, and 0.87 ± 0.07, respectively). There was a significant decrease (p ≤ 0.01 - 0.001) in SBP and MAP with 100 mg/kg CAPE 1 and 75 mg/kg CAPE 2 treatment in hypertension as well as with nifedipine (p ≤ 0.001) treatment. Epinephrine-induced hypertension in anesthetized cats was significantly and dose-dependently inhibited (p < 0.05 - 0.001) by 25-100 mg/ml CAPE 1 and 37.5-75 mg/ml CAPE 2. CAPE administration had no deleterious effect (p > 0.05) on full blood count, liver and kidney function, and urine composition in hypertensive rats. Conclusion The aqueous leaf extracts of Annona muricata, Persea americana, and their combination products possess antihypertensive properties, with combination products showing synergism and safety with use.
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Abstract
Introduction: Despite the improved treatment protocol of hypertension, the magnitude of the disease and its related burden remains raised. Hypertension makes up the leading cause of stroke, kidney disease, arterial disease, eye disease, and cardiovascular disease (CVD) growth. Areas covered: This review provides the overview of the role of dietary salt and alcohol use reduction in the management of hypertension, a brief history of alcohol, the vascular endothelium functions, the effects of alcohol use on blood pressure (BP), the mechanisms of alcohol, brief history of salt, the effects of dietary salt intake on BP, and the mechanisms of salt. Expert opinion: Studies found that high dietary salt intake and heavy alcohol consumption have a major and huge impact on BP while both of them have been identified to increase BP. Also, they raise the risk of hypertension-related morbidity and mortality in advance. On the other way, the dietary salt and alcohol use reduction in the management of hypertension are significant in the control of BP and its related morbidity and mortality. Further, studies suggested that the dietary salt and alcohol use reductions are the cornerstone in the management of hypertension due to their significance as part of comprehensive lifestyle modifications.
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Affiliation(s)
- Addisu Dabi Wake
- Nursing Department, College of Health Sciences, Arsi University , Asella, Ethiopia
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7
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Valenzuela PL, Carrera-Bastos P, Gálvez BG, Ruiz-Hurtado G, Ordovas JM, Ruilope LM, Lucia A. Lifestyle interventions for the prevention and treatment of hypertension. Nat Rev Cardiol 2020; 18:251-275. [PMID: 33037326 DOI: 10.1038/s41569-020-00437-9] [Citation(s) in RCA: 182] [Impact Index Per Article: 36.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/24/2020] [Indexed: 02/07/2023]
Abstract
Hypertension affects approximately one third of the world's adult population and is a major cause of premature death despite considerable advances in pharmacological treatments. Growing evidence supports the use of lifestyle interventions for the prevention and adjuvant treatment of hypertension. In this Review, we provide a summary of the epidemiological research supporting the preventive and antihypertensive effects of major lifestyle interventions (regular physical exercise, body weight management and healthy dietary patterns), as well as other less traditional recommendations such as stress management and the promotion of adequate sleep patterns coupled with circadian entrainment. We also discuss the physiological mechanisms underlying the beneficial effects of these lifestyle interventions on hypertension, which include not only the prevention of traditional risk factors (such as obesity and insulin resistance) and improvements in vascular health through an improved redox and inflammatory status, but also reduced sympathetic overactivation and non-traditional mechanisms such as increased secretion of myokines.
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Affiliation(s)
| | - Pedro Carrera-Bastos
- Centre for Primary Health Care Research, Lund University/Region Skane, Skane University Hospital, Malmö, Sweden
| | - Beatriz G Gálvez
- Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain
| | - Gema Ruiz-Hurtado
- Research Institute of the Hospital Universitario 12 de Octubre (imas12), Madrid, Spain.,CIBER-CV, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - José M Ordovas
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.,IMDEA Alimentacion, Madrid, Spain
| | - Luis M Ruilope
- Research Institute of the Hospital Universitario 12 de Octubre (imas12), Madrid, Spain.,CIBER-CV, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Alejandro Lucia
- Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain. .,Research Institute of the Hospital Universitario 12 de Octubre (imas12), Madrid, Spain.
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8
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Peng J, Wang H, Rong X, He L, Xiangpen L, Shen Q, Peng Y. Cerebral Hemorrhage and Alcohol Exposure: A Review. Alcohol Alcohol 2019; 55:20-27. [PMID: 31845978 DOI: 10.1093/alcalc/agz087] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 08/29/2019] [Accepted: 09/17/2019] [Indexed: 01/20/2023] Open
Abstract
Abstract
Aims
To investigate the dose–response relationships between alcohol and intracerebral hemorrhage (ICH), the impact of alcohol on the outcome of ICH and possible mechanisms underlying hypertensive ICH (HICH) caused by heavy drinking.
Methods
Literature search from 1985 to August 2019 in the PubMed database.
Results
The relationship between low-middle alcohol consumption and ICH remains controversial for various reasons, whereas chronic heavy drinking increases the incidence of ICH and exerts worse outcome. More attention is needed to clarify the characteristics of chronic alcohol intake and binge drinking. Chronic alcohol abuse tends to elevates blood pressure, resulting in increased occurrence of HICH and exaggerated HICH-contributed brain injury.
Conclusion
It is important to develop strategies to promote reasonable intake categories, prevent alcoholism and thus reduce the risk of ICH.
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Affiliation(s)
- Jialing Peng
- Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. No. 33 Yinfeng Road, Guangzhou 510828
| | - Hongxuan Wang
- Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. No. 33 Yinfeng Road, Guangzhou 510828
| | - Xiaoming Rong
- Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. No. 33 Yinfeng Road, Guangzhou 510828
| | - Lei He
- Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. No. 33 Yinfeng Road, Guangzhou 510828
| | - L Xiangpen
- Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. No. 33 Yinfeng Road, Guangzhou 510828
| | - Qingy Shen
- Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. No. 33 Yinfeng Road, Guangzhou 510828
| | - Ying Peng
- Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. No. 33 Yinfeng Road, Guangzhou 510828
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. No. 33 Yinfeng Road, Guangzhou 510828
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9
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Yarlioglues M, Yalcinkaya D, Oksuz F, Celik IE, Duran M, Murat SN. Possible Effect of Alcohol Consumption on Aortic Dilatation by Inducing Renin-Angiotensin-Aldosterone System. Angiology 2019; 70:978-979. [PMID: 31216859 DOI: 10.1177/0003319719857381] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Mikail Yarlioglues
- 1 Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey
| | - Damla Yalcinkaya
- 1 Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey
| | - Fatih Oksuz
- 1 Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey
| | - Ibrahim Etem Celik
- 1 Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey
| | - Mustafa Duran
- 1 Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey
| | - Sani Namik Murat
- 1 Department of Cardiology, Ankara Education and Research Hospital, Ankara, Turkey
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Abstract
Abstract
Introduction According to the data obtained in the EZOP Poland study (2015), the prevalence of alcohol dependence in lifetime in Poland amounts to about 2.2% of the population, entailing enormous social, family and personal harm, including health damage. It is estimated that about 72% of alcohol-dependent patients complain about one or more problems related to the sexual sphere, which may result from both the development of somatic complications in the course of alcohol dependence, and from psychiatric complications that themselves can lead to sexual dysfunction. There are reports and clinical observations indicating that the occurrence of sexual dysfunction (SD) can affect the shortening or interruption of the period of abstinence.
Aim The aim of this work is to show sexual dysfunctions in alcohol-dependent men and to discuss the factors that may affect the occurrence of the above-mentioned dysfunctions.
Material and methods The available literature was reviewed using Medline, Google Scholar and ScienceDirect browsers by entering the keywords: alcohol dependence, sexual dysfunction, comorbidity, alcohol-caused diseases and time descriptors: 1979-2016.
Results
• Alcohol dependence is associated with the occurrence of various types of sexual dysfunctions (SD).
• The diagnosis of SD should take into account all possible causes that may lead to the development of SD in this group of patients, including the comorbidity of somatic diseases or the negative impact of drugs on sexual function.
• Occurrence of SD is connected with a higher risk of abstinence interruption.
• There is a need to carry out more research in order to better understand the relationship between alcohol dependence and the prevalence of sexual dysfunctions.
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Zaidi Touis L, Bolbrinker J, Riemer TG, Kreutz R. Moderation of alcohol consumption as a recommendation in European hypertension management guidelines: a survey on awareness, screening and implementation among European physicians. BMJ Open 2018; 8:e022026. [PMID: 30344170 PMCID: PMC6196817 DOI: 10.1136/bmjopen-2018-022026] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES Moderation of alcohol consumption is included as a class I, level of evidence A recommendation in the current European guidelines for the management of hypertension. We investigated its awareness and self-reported implementation among European physicians across different specialties and workplaces. DESIGN AND SETTING A cross-sectional survey study conducted in two annual German meetings (German Society of Cardiology and the German Society of Internal Medicine) and two annual European meetings (European Society of Hypertension and European Society Cardiology) in 2015. PARTICIPANTS 1064 physicians attending the European meetings were interviewed including 52.1% cardiologists, 29.2% internists and 8.8% general practitioners. MAIN OUTCOME MEASURES Physician screening of alcohol consumption, awareness and self-implementation of the recommendation of the current European guidelines about moderation of alcohol consumption for the management of hypertension. RESULTS Overall, 81.9% of physicians reported to generally quantify alcohol consumption in patients with hypertension. However, only 28.6% and 14.5% of participants reported screening alcohol consumption in their patients with newly detected or treatment-resistant hypertension. Physicians recommended a maximum alcohol intake of 13.1±11.7 g/day for women (95% CI 12.3 to 13.8) and 19.9±15.6 g/day for men (95% CI 18.8 to 20.9). In case of moderate to high alcohol consumption, 10.3% would manage only hypertension without addressing alcohol consumption, while 3.7% of the physicians would do so in case of alcohol dependence (p<0.001). CONCLUSIONS The average amount of alcohol intake per day recommended by European physicians in this survey was in agreement with the guidelines. The low number of physicians that screen for alcohol consumption in patients with newly detected and with treatment-resistant hypertension indicates an important deficit in the management of hypertension.
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Affiliation(s)
- Laila Zaidi Touis
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut fur Klinische Pharmakologie und Toxikologie, Berlin, Germany
| | - Juliane Bolbrinker
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut fur Klinische Pharmakologie und Toxikologie, Berlin, Germany
| | - Thomas Günther Riemer
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut fur Klinische Pharmakologie und Toxikologie, Berlin, Germany
| | - Reinhold Kreutz
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut fur Klinische Pharmakologie und Toxikologie, Berlin, Germany
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Naik VD, Davis-Anderson K, Subramanian K, Lunde-Young R, Nemec MJ, Ramadoss J. Mechanisms Underlying Chronic Binge Alcohol Exposure-Induced Uterine Artery Dysfunction in Pregnant Rat. Alcohol Clin Exp Res 2018; 42:682-690. [PMID: 29363778 DOI: 10.1111/acer.13602] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 01/16/2018] [Indexed: 01/17/2023]
Abstract
BACKGROUND A cardinal feature of fetal alcohol syndrome is growth restriction. Maternal uterine artery adaptations to pregnancy correlate with birthweight and survival. We hypothesized that gestational binge alcohol exposure impairs maternal uterine vascular function, affecting endothelial nitric oxide (NO)-mediated vasodilation. METHODS Pregnant rats grouped as pair-fed control or binge alcohol exposed received a once-daily, orogastric gavage of isocaloric maltose-dextrin or alcohol, respectively. On gestational day 20, primary uterine arteries were isolated, cannulated, and connected to a pressure transducer, and functional studies were conducted by dual-chamber arteriography. Uterine arteries maintained at constant intramural pressure (90 mm Hg) were maximally constricted with thromboxane, and a dose-response for acetylcholine (Ach) was recorded. RESULTS The alcohol group exhibited significantly impaired endothelium-dependent, Ach-induced uterine artery relaxation (↓∼30%). Subsequently, a dose-response was recorded following inhibition of endothelium-derived hyperpolarizing factor (apamin and TRAM-34) and prostacyclin (indomethacin). Ach-induced relaxation in the pair-fed control decreased by ~46%, and interestingly, relaxation in alcohol group further decreased by an additional ~48%, demonstrating that gestational binge alcohol impairs the NO system in the primary uterine artery. An endothelium-independent sodium nitroprusside effect was not observed. Immunoblotting indicated that alcohol decreased the level of endothelial excitatory P-Ser1177 endothelial NO synthase (eNOS) (p < 0.05) and total eNOS expression (p < 0.05) compared to both the normal and pair-fed controls. P-Ser1177 eNOS level was also confirmed by immunofluorescence imaging. CONCLUSIONS This is the first study to demonstrate maternal binge alcohol consumption during pregnancy disrupts uterine artery vascular function via impairment of the eNOS vasodilatory system.
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Affiliation(s)
- Vishal D Naik
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
| | - Katie Davis-Anderson
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
| | - Kaviarasan Subramanian
- Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
| | - Raine Lunde-Young
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
| | - Matthew J Nemec
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
| | - Jayanth Ramadoss
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas
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13
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Leal S, Ricardo Jorge DO, Joana B, Maria S, Isabel S. Heavy Alcohol Consumption Effects on Blood Pressure and on Kidney Structure Persist After Long-Term Withdrawal. Kidney Blood Press Res 2017; 42:664-675. [DOI: 10.1159/000482022] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 08/07/2017] [Indexed: 11/19/2022] Open
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14
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Association of alcohol consumption pattern with risk of hypertension in Korean adults based on the 2010-2012 KNHANES. Alcohol 2016; 54:17-22. [PMID: 27565751 DOI: 10.1016/j.alcohol.2016.05.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2015] [Revised: 04/27/2016] [Accepted: 05/23/2016] [Indexed: 11/23/2022]
Abstract
We examined the association between alcohol-drinking pattern and hypertension in Korean adults. This cross-sectional study included 15,052 participants (7054 men and 7998 women) who were included in the 2010-2012 Korean National Health and Nutrition Examination Survey (KNHANES). We categorized alcohol-drinking patterns into three groups based on the Alcohol Use Disorders Identification Test (AUDIT) score: low-risk (score: 0-7), intermediate-risk (score: 8-14), and high-risk (score: ≥15). Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or current use of anti-hypertensive medications. In the study population, 25.2% of men and 4.6% of women were high-risk drinkers. Hypertension prevalence was 30.8% in men and 20.6% in women. Of the total population, 13.8% of men and 13.6% of women were using anti-hypertensive drugs. Age-adjusted hypertension prevalence was 30.8, 40.9, and 45.3% in men, and 24.6, 27.0, and 32.3% in women in the low-, intermediate-, and high-risk drinking group, respectively. Compared to the low-risk drinking group, the prevalence ratio (95% confidence interval [CI]) for hypertension was 1.664 (1.4331.933) and 2.070 (1.772-2.418) for men and 1.012 (0.774-1.323) and 1.650 (1.080-2.522) for women in the intermediate- and high-risk drinking group, respectively, after adjusting for age and other confounding factors. In conclusion, our study suggests high-risk drinking appears to be associated with a higher risk of hypertension in men and women.
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Ansari RA, Husain K, Rizvi SAA. Role of Transcription Factors in Steatohepatitis and Hypertension after Ethanol: The Epicenter of Metabolism. Biomolecules 2016; 6:29. [PMID: 27348013 PMCID: PMC5039415 DOI: 10.3390/biom6030029] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 05/25/2016] [Accepted: 06/08/2016] [Indexed: 02/07/2023] Open
Abstract
Chronic alcohol consumption induces multi-organ damage, including alcoholic liver disease (ALD), pancreatitis and hypertension. Ethanol and ethanol metabolic products play a significant role in the manifestation of its toxicity. Ethanol metabolizes to acetaldehyde and produces reduced nicotinamide adenine dinucleotide (NADH) by cytosolic alcohol dehydrogenase. Ethanol metabolism mediated by cytochrome-P450 2E1 causes oxidative stress due to increased production of reactive oxygen species (ROS). Acetaldehyde, increased redox cellular state and ROS activate transcription factors, which in turn activate genes for lipid biosynthesis and offer protection of hepatocytes from alcohol toxicity. Sterol regulatory element binding proteins (SREBPs) and peroxisome proliferator activated-receptors (PPARs) are two key lipogenic transcription factors implicated in the development of fatty liver in alcoholic and non-alcoholic steatohepatitis. SREBP-1 is activated in the livers of chronic ethanol abusers. An increase in ROS activates nuclear factor erythroid-2-related factor-2 (Nrf2) and hypoxia inducible factor (HIF) to provide protection to hepatocytes from ethanol toxicity. Under ethanol exposure, due to increased gut permeability, there is release of gram-negative bacteria-derived lipopolysaccharide (LPS) from intestine causing activation of immune response. In addition, the metabolic product, acetaldehyde, modifies the proteins in hepatocyte, which become antigens inviting auto-immune response. LPS activates macrophages, especially the liver resident macrophages, Kupffer cells. These Kupffer cells and circulating macrophages secrete various cytokines. The level of tumor necrosis factor-α (TNFα), interleukin-1beta (IL-1β), IL-6, IL-8 and IL-12 have been found elevated among chronic alcoholics. In addition to elevation of these cytokines, the peripheral iron (Fe(2+)) is also mobilized. An increased level of hepatic iron has been observed among alcoholics. Increased ROS, IL-1β, acetaldehyde, and increased hepatic iron, all activate nuclear factor-kappa B (NF-κB) transcription factor. Resolution of increased reactive oxygen species requires increased expression of genes responsible for dismutation of increased ROS which is partially achieved by IL-6 mediated activation of signal transducers and activators of transcription 3 (STAT3). In addition to these transcription factors, activator protein-1 may also be activated in hepatocytes due to its association with resolution of increased ROS. These transcription factors are central to alcohol-mediated hepatotoxicity.
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Affiliation(s)
- Rais A Ansari
- Department of Pharmaceutical Sciences, College of Pharmacy, Health Professions Division, Nova Southeastern University, 3200 S University Drive, Fort Lauderdale, FL 33328, USA.
| | - Kazim Husain
- Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, P.O. Box 7004, Ponce, PR 00732-2575, USA.
| | - Syed A A Rizvi
- Department of Pharmaceutical Sciences, College of Pharmacy, Health Professions Division, Nova Southeastern University, 3200 S University Drive, Fort Lauderdale, FL 33328, USA.
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16
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Santilli F, D'Ardes D, Davì G. Oxidative stress in chronic vascular disease: From prediction to prevention. Vascul Pharmacol 2015; 74:23-37. [DOI: 10.1016/j.vph.2015.09.003] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 09/04/2015] [Accepted: 09/08/2015] [Indexed: 12/14/2022]
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Husain K, Hernandez W, Ansari RA, Ferder L. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis. World J Biol Chem 2015; 6:209-217. [PMID: 26322175 PMCID: PMC4549761 DOI: 10.4331/wjbc.v6.i3.209] [Citation(s) in RCA: 231] [Impact Index Per Article: 23.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 05/15/2015] [Accepted: 06/19/2015] [Indexed: 02/05/2023] Open
Abstract
Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice.
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Husain K, Suarez E, Isidro A, Hernandez W, Ferder L. Effect of paricalcitol and enalapril on renal inflammation/oxidative stress in atherosclerosis. World J Biol Chem 2015; 6:240-248. [PMID: 26322179 PMCID: PMC4549765 DOI: 10.4331/wjbc.v6.i3.240] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2015] [Revised: 03/25/2015] [Accepted: 06/11/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in ApoE-knock out mice.
METHODS: Animals treated for 4 mo as group (1) ApoE-knock out plus vehicle, group (2) ApoE-knock out plus paricalcitol (200 ng thrice a week), (3) ApoE-knock out plus enalapril (30 mg/L), (4) ApoE-knock out plus paricalcitol plus enalapril and (5) normal. Blood pressure (BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses.
RESULTS: ApoE-deficient mice developed high BP (127 ± 3 mmHg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22phox, manganese-superoxide dismutase, inducible nitric oxide synthase (NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, CuZn-SOD and eNOS levels significantly depleted in ApoE-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in ApoE-knock out animals.
CONCLUSION: Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals.
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Wang Y, Li Y, Shen Q, Li X, Lu J, Li X, Yin D, Peng Y. Valsartan blocked alcohol-induced, Toll-like receptor 2 signaling-mediated inflammation in human vascular endothelial cells. Alcohol Clin Exp Res 2015; 38:2529-40. [PMID: 25346502 DOI: 10.1111/acer.12532] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Accepted: 07/22/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND Alcohol consumption induces inflammatory damage in vessels, and the underlying mechanism is unclear. Valsartan, as one of the angiotensin receptor blockers (ARBs), plays a role in the inhibition of inflammatory reactions in vascular dysfunction. This study is to investigate the role of Toll-like receptor 2 (TLR2) in alcohol-induced inflammatory damage in vascular endothelial cells in vitro and to explore the protective effect of valsartan on alcohol-induced and TLR2-mediated inflammatory damage. METHODS The human umbilical vein cell line (EA.hy926) were exposed to alcohol at 0 to 80 mM for 0 to 48 hours with or without valsartan pretreatment. The expression of TLR2 signaling, including TLR2, tumor necrosis factor receptor associated factor 6 (TRAF-6) and nuclear factor kappa B (NF-κB) p65 were detected by Western blot. The levels of proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were determined by ELISA. To confirm the role of TLR2, we functionally up-regulated or down-regulated TLR2 by using TLR2 agonist or TLR2 small interfering RNA (siRNA), respectively. To further investigate the mechanism of alcohol on renin-angiotensin system, we detected the expression of angiotensin II receptor type 1 (AGTR1) in protein levels. RESULTS The expression of TLR2, TRAF-6, NF-κB p65, and the proinflammatory cytokines, TNF-α and IL-6, were significantly increased after alcohol exposure in EA.hy926 endothelial cells. This was enhanced by TLR2 agonist, and was inhibited by TLR2 siRNA transfection. The pretreatment of valsartan resulted in an inhibition of TLR2 signaling and proinflammatory cytokines. The expression of AGTR1 was up-regulated after alcohol exposure, and was blocked by valsartan pretreatment. CONCLUSIONS TLR2 signaling-mediated alcohol induced inflammatory response in human vascular epithelial cells in vitro, which was inhibited by valsartan.
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Affiliation(s)
- Yushu Wang
- Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
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Passaglia P, Ceron CS, Mecawi AS, Antunes-Rodrigues J, Coelho EB, Tirapelli CR. Angiotensin type 1 receptor mediates chronic ethanol consumption-induced hypertension and vascular oxidative stress. Vascul Pharmacol 2015; 74:49-59. [PMID: 25872164 DOI: 10.1016/j.vph.2015.04.002] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 03/09/2015] [Accepted: 04/04/2015] [Indexed: 02/06/2023]
Abstract
OBJECTIVES We hypothesized that chronic ethanol intake enhances vascular oxidative stress and induces hypertension through renin-angiotensin system (RAS) activation. METHODS AND RESULTS Male Wistar rats were treated with ethanol (20% v/v). The increase in blood pressure induced by ethanol was prevented by losartan (10mg/kg/day; p.o. gavage), a selective AT1 receptor antagonist. Chronic ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels and serum aldosterone levels. No differences on plasma osmolality and sodium or potassium levels were detected after treatment with ethanol. Ethanol consumption did not alter ACE activity, as well as the levels of ANG I and ANG II in the rat aorta or mesenteric arterial bed (MAB). Ethanol induced systemic and vascular oxidative stress (aorta and MAB) and these effects were prevented by losartan. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol was prevented by losartan. Ethanol intake did not alter protein expression of ACE, AT1 or AT2 receptors in both aorta and MAB. Aortas from ethanol-treated rats displayed decreased ERK1/2 phosphorylation and increased protein expression of SAPK/JNK. These responses were prevented by losartan. MAB from ethanol-treated rats displayed reduced phosphorylation of p38MAPK and ERK1/2 and losartan did not prevent these responses. CONCLUSIONS Our study provides novel evidence that chronic ethanol intake increases blood pressure, induces vascular oxidative stress and decreases nitric oxide (NO) bioavailability through AT1-dependent mechanisms.
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Affiliation(s)
- Patrícia Passaglia
- Programa de pós-graduação em Toxicologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil; Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil
| | - Carla S Ceron
- Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil
| | - André S Mecawi
- Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil
| | | | - Eduardo B Coelho
- Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil
| | - Carlos R Tirapelli
- Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil.
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Antihypertensive effect of radix paeoniae alba in spontaneously hypertensive rats and excessive alcohol intake and high fat diet induced hypertensive rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 2015:731237. [PMID: 25784949 PMCID: PMC4345252 DOI: 10.1155/2015/731237] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Revised: 01/21/2015] [Accepted: 01/22/2015] [Indexed: 02/07/2023]
Abstract
Radix Paeoniae Alba (Baishao, RPA) has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD-) induced hypertensive rats and spontaneously hypertensive rats (SHR) was constantly received either RPA extract (25 or 75 mg/kg) or captopril (15 mg/kg) all along the experiments. As a result, RPA extract (75 mg/kg) could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT) and aspartate transaminase (AST) in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO) and endothelin (ET) levels.
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Gonzaga NA, Mecawi AS, Antunes-Rodrigues J, De Martinis BS, Padovan CM, Tirapelli CR. Ethanol withdrawal increases oxidative stress and reduces nitric oxide bioavailability in the vasculature of rats. Alcohol 2015; 49:47-56. [PMID: 25557835 DOI: 10.1016/j.alcohol.2014.12.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2014] [Revised: 10/31/2014] [Accepted: 12/04/2014] [Indexed: 01/17/2023]
Abstract
We analyzed the effects of ethanol withdrawal on the vascular and systemic renin-angiotensin system (RAS) and vascular oxidative stress. Male Wistar rats were treated with ethanol 3-9% (v/v) for a period of 21 days. Ethanol withdrawal was induced by abrupt discontinuation of the treatment. Experiments were performed 48 h after ethanol discontinuation. Rats from the ethanol withdrawal group showed decreased exploration of the open arms of the elevated-plus maze (EPM) and increased plasma corticosterone levels. Ethanol withdrawal significantly increased systolic blood pressure and plasma angiotensin II (ANG II) levels without an effect on plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, or plasma angiotensin I (ANG I) levels. No differences in vascular ANG I, ANG II levels, and ACE activity/expression and AT1 and AT2 receptor expression were detected among the experimental groups. Plasma osmolality, as well as plasma sodium, potassium, and glucose levels were not affected by ethanol withdrawal. Ethanol withdrawal induced systemic and vascular oxidative stress, as evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels and the vascular generation of superoxide anion. Ethanol withdrawal significantly decreased plasma and vascular nitrate/nitrite levels. Major new findings of the present study are that ethanol withdrawal induces vascular oxidative stress and reduces nitric oxide (NO) levels in the vasculature. Additionally, our study provides novel evidence that ethanol withdrawal does not affect the vascular ANG II generating system while stimulating systemic RAS. These responses could predispose individuals to the development of cardiovascular diseases.
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Affiliation(s)
- Natalia A Gonzaga
- Programa de pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil; Escola de Enfermagem de Ribeirão Preto, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, USP, Ribeirão Preto, São Paulo, Brazil
| | - André S Mecawi
- Faculdade de Medicina de Ribeirão Preto, Departamento de Fisiologia, USP, Ribeirão Preto, São Paulo, Brazil
| | - José Antunes-Rodrigues
- Faculdade de Medicina de Ribeirão Preto, Departamento de Fisiologia, USP, Ribeirão Preto, São Paulo, Brazil
| | - Bruno S De Martinis
- Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil
| | - Claudia M Padovan
- Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil
| | - Carlos R Tirapelli
- Escola de Enfermagem de Ribeirão Preto, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, USP, Ribeirão Preto, São Paulo, Brazil.
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Silva SM, Silva S, Meireles M, Leal S. nNOS is involved in cardiac remodeling induced by chronic ethanol consumption. Toxicology 2015; 329:98-105. [PMID: 25598224 DOI: 10.1016/j.tox.2015.01.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Revised: 01/12/2015] [Accepted: 01/13/2015] [Indexed: 01/12/2023]
Abstract
Chronic ethanol consumption has deleterious effects on the cardiovascular system by directly damaging the myocardial structure and/or by neurohormonal activation. Moreover, nitric oxide (NO) derived from neuronal NO synthase (nNOS) seems to be important to balance the harmful effects of ethanol consumption, because it influences several aspects of cardiac physiology and attenuates pathological cardiac remodeling. However, the impact of chronic ethanol consumption on nNOS expression is unknown. We address this subject in the present study by evaluating whether chronic ethanol consumption induces cardiac remodeling and hypertension, and if these changes are associated with alterations in the expression of nNOS. Male Wistar rats were examined after ingesting a 20% alcohol solution for 6 months. Blood alcohol concentration and brain natriuretic peptide (BNP) levels were measured. The cardiac remodeling was assessed by histomorphometric analysis and the nNOS expression was evaluated by immunofluorescence and western blot analysis. Our results show that chronic ethanol consumption induces cardiac remodeling, namely thinning of left ventricular wall, cardiomyocyte hypertrophy and increased fibrosis, and elevations of arterial blood pressure. They also show that in rats fed with ethanol for 6 months, the circulating BNP levels had decreased as well as the expression of nNOS in left ventricle cardiomyocytes. These findings suggest that the effects of chronic ethanol consumption on BNP levels and/or on nNOS expression in cardiomyocytes may contribute to aggravate the cardiac remodeling and leads to progression of cardiomyopathy.
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Affiliation(s)
- Susana M Silva
- Department of Anatomy, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; Center of Experimental Morphology (CME), Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Rua Dr Plácido da Costa, s/n, 4200-450 Porto, Portugal
| | - Sérgio Silva
- Department of Anatomy, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; Center of Experimental Morphology (CME), Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; Department of Internal Medicine, Centro Hospitalar de S. João (CHSJ), Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Manuela Meireles
- Center for Health Technology and Services Research (CINTESIS), Rua Dr Plácido da Costa, s/n, 4200-450 Porto, Portugal; Department of Biochemistry, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Sandra Leal
- Department of Anatomy, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; Center of Experimental Morphology (CME), Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; CESPU, IINFACTS, Departamento de Ciências do ISCS-N, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal.
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Baptista RDFF, Chies AB, Taipeiro EDF, Cordellini S. Endothelial AT₁ and AT₂ pathways in aortic responses to angiotensin II after stress and ethanol consumption in rats. Stress 2014; 17:512-9. [PMID: 25238020 DOI: 10.3109/10253890.2014.966262] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Stress and ethanol are important cardiovascular risk factors. Their vascular and blood pressure (BP) effects were evaluated alone and in combination. Adult male Wistar rats (8-10 per group) were separated into control, ethanol (ethanol 20% in drinking water for 6 weeks), stress (restraint 1 h/d 5 d/week for 6 weeks), and ethanol/stress (in combination) groups. Systolic BP was evaluated weekly. Concentration-response curves for contractile responses to angiotensin II in the absence and the presence of losartan (AT1-blocker), PD123-319 (AT2-blocker), L-NAME (nitric oxide synthase inhibitor), or indomethacin (cyclooxygenase inhibitor) were obtained in isolated intact and endothelium-denuded aortas. Effective concentration 50% (EC50) and maximum response (MR) were compared among groups using MANOVA/Tukey tests. Stress and stress plus ethanol increased BP. Ethanol and stress, alone and in combination, did not alter angiotensin responses of intact aortas. PD123-319 decreased MR to angiotensin II in intact aortas from the ethanol and ethanol/stress groups relative to control in the presence of PD123-319. Losartan increased MR to angiotensin II in intact aortas from the stress and ethanol/stress groups relative to control in the presence of losartan. None of the protocols altered angiotensin responses of denuded aortas. Neither indomethacin nor L-NAME altered angiotensin responses of intact aortas from the experimental groups. Thus ethanol and ethanol plus stress may alter endothelial signaling via AT1-receptors, without changing systemic BP. Stress and stress plus ethanol may alter endothelial signaling via AT2-receptors, and thereby increase BP. Knowledge of such vascular changes induced by stress and/or ethanol may contribute to understanding adverse cardiovascular effects of stress and ethanol consumption in humans.
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MESH Headings
- Alcohol Drinking/adverse effects
- Alcohol Drinking/metabolism
- Alcohol Drinking/physiopathology
- Angiotensin II/pharmacology
- Angiotensin II Type 1 Receptor Blockers/pharmacology
- Angiotensin II Type 2 Receptor Blockers/pharmacology
- Animals
- Antioxidants/metabolism
- Blood Pressure/drug effects
- Corticosterone/blood
- Dose-Response Relationship, Drug
- Endothelium, Vascular/drug effects
- Endothelium, Vascular/metabolism
- Endothelium, Vascular/physiopathology
- Enzyme Inhibitors/pharmacology
- Ethanol/toxicity
- Hypertension/etiology
- Hypertension/metabolism
- Hypertension/physiopathology
- Male
- Rats, Wistar
- Receptor, Angiotensin, Type 1/agonists
- Receptor, Angiotensin, Type 1/metabolism
- Receptor, Angiotensin, Type 2/agonists
- Receptor, Angiotensin, Type 2/metabolism
- Restraint, Physical
- Risk Factors
- Signal Transduction/drug effects
- Stress, Psychological/complications
- Stress, Psychological/metabolism
- Stress, Psychological/physiopathology
- Time Factors
- Vasoconstriction/drug effects
- Vasoconstrictor Agents/pharmacology
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Husain K, Ansari RA, Ferder L. Alcohol-induced hypertension: Mechanism and prevention. World J Cardiol 2014; 6:245-252. [PMID: 24891935 PMCID: PMC4038773 DOI: 10.4330/wjc.v6.i5.245] [Citation(s) in RCA: 191] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Epidemiological, preclinical and clinical studies established the association between high alcohol consumption and hypertension. However the mechanism through which alcohol raises blood pressure remains elusive. Several possible mechanisms have been proposed such as an imbalance of the central nervous system, impairment of the baroreceptors, enhanced sympathetic activity, stimulation of the renin-angiotensin-aldosterone system, increased cortisol levels, increased vascular reactivity due to increase in intracellular calcium levels, stimulation of the endothelium to release vasoconstrictors and loss of relaxation due to inflammation and oxidative injury of the endothelium leading to inhibition of endothelium-dependent nitric oxide production. Loss of relaxation due to inflammation and oxidative injury of the endothelium by angiotensin II leading to inhibition of endothelium-dependent nitric oxide production is the major contributors of the alcohol-induced hypertension. For the prevention of alcohol-induced hypertension is to reduce the amount of alcohol intake. Physical conditioning/exercise training is one of the most important strategies to prevent/treat chronic alcohol-induced hypertension on physiological basis. The efficacious pharmacologic treatment includes the angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs) which have antioxidant activity and calcium channel blockers. The most effective prevention and treatment of alcohol-induced hypertension is physical exercise and the use of ACE inhibitors or ARBs in the clinic
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Marchi KC, Muniz JJ, Tirapelli CR. Hypertension and chronic ethanol consumption: What do we know after a century of study? World J Cardiol 2014; 6:283-294. [PMID: 24944758 PMCID: PMC4062120 DOI: 10.4330/wjc.v6.i5.283] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 03/11/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
The influences of life habits on the cardiovascular system may have important implications for public health, as cardiovascular diseases are among the leading causes of shorter life expectancy worldwide. A link between excessive ethyl alcohol (ethanol) consumption and arterial hypertension was first suggested early last century. Since then, this proposition has received considerable attention. Support for the concept of ethanol as a cause of hypertension derives from several epidemiologic studies demonstrating that in the general population, increased blood pressure is significantly correlated with ethanol consumption. Although the link between ethanol consumption and hypertension is well established, the mechanism through which ethanol increases blood pressure remains elusive. Possible mechanisms underlying ethanol-induced hypertension were proposed based on clinical and experimental observations. These mechanisms include an increase in sympathetic nervous system activity, stimulation of the renin-angiotensin-aldosterone system, an increase of intracellular Ca2+ in vascular smooth muscle, increased oxidative stress and endothelial dysfunction. The present report reviews the relationship between ethanol intake and hypertension and highlights some mechanisms underlying this response. These issues are of interest for the public health, as ethanol consumption contributes to blood pressure elevation in the population.
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Gonzaga NA, Callera GE, Yogi A, Mecawi AS, Antunes-Rodrigues J, Queiroz RH, Touyz RM, Tirapelli CR. Acute ethanol intake induces mitogen-activated protein kinase activation, platelet-derived growth factor receptor phosphorylation, and oxidative stress in resistance arteries. J Physiol Biochem 2014; 70:509-23. [PMID: 24733165 DOI: 10.1007/s13105-014-0331-6] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Accepted: 03/10/2014] [Indexed: 12/16/2022]
Abstract
In the present study, we investigated the role of angiotensin type I (AT1) receptor in reactive oxygen species (ROS) generation and mitogen-activated protein kinases (MAPK) activation induced by acute ethanol intake in resistance arteries. We also evaluated the effect of ethanol on platelet-derived growth factor receptors (PDGF-R) phosphorylation and the role of this receptor on ROS generation by ethanol. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. Acute ethanol intake did not alter angiotensin I or angiotensin II levels in the rat mesenteric arterial bed (MAB). Ethanol induced vascular oxidative stress, and this response was not prevented by losartan (10 mg/kg; p.o. gavage), a selective AT1 receptor antagonist. MAB from ethanol-treated rats displayed increased SAPK/JNK and PDGF-R phosphorylation, responses that were not prevented by losartan. The phosphorylation levels of protein kinase B (Akt) and eNOS were not affected by acute ethanol intake. MAB nitrate levels and the reactivity of this tissue to acetylcholine, phenylephrine, and sodium nitroprusside were not affected by ethanol intake. Ethanol did not alter plasma antioxidant capacity, the levels of reduced glutathione, or the activities of superoxide dismutase and catalase in the rat MAB. Short-term effects of ethanol (50 mmol/l) were evaluated in vascular smooth muscle cells (VSMC) isolated from rat MAB. Ethanol increased ROS generation, and this response was not affected by AG1296, a PDGF-R inhibitor, or losartan. Finally, ethanol did not alter MAPK or PDGF-R phosphorylation in cultured VSMC. Our study provides novel evidence that acute ethanol intake induces ROS generation, PDGF-R phosphorylation, and MAPK activation through AT(1)-independent mechanisms in resistance arteries in vivo. MAPK and PDGF-R play a role in vascular signaling and cardiovascular diseases and may contribute to the vascular pathobiology of ethanol.
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Affiliation(s)
- Natália A Gonzaga
- Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil
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Baptista RDFF, Taipeiro EDF, Queiroz RHC, Chies AB, Cordellini S. Stress alone or associated with ethanol induces prostanoid release in rat aorta via alpha2-Adrenoceptor. Arq Bras Cardiol 2014; 102:211-8. [PMID: 24676223 PMCID: PMC3987321 DOI: 10.5935/abc.20140015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2013] [Accepted: 10/02/2013] [Indexed: 12/29/2022] Open
Abstract
Background Stress and ethanol are both, independently, important cardiovascular risk
factors. Objective To evaluate the cardiovascular risk of ethanol consumption and stress exposure,
isolated and in association, in male adult rats. Methods Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6
weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and
stress/ethanol. Concentration-responses curves to noradrenaline - in the absence
and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were
determined in thoracic aortas with and without endothelium. EC50 and maximum
response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Results Either stress or stress in association with ethanol consumption increased the
noradrenaline maximum responses in intact aortas. This hyper-reactivity was
eliminated by endothelium removal or by the presence of either indomethacin or
yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol
consumption did not alter the reactivity to noradrenaline. The phenylephrine
responses in aortas both with and without endothelium also remained unaffected
regardless of protocol. Conclusion Chronic stress increased rat aortic responses to noradrenaline. This effect is
dependent upon the vascular endothelium and involves the release of
vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors.
Moreover, chronic ethanol consumption appeared to neither influence noradrenaline
responses in rat thoracic aorta, nor did it modify the increase of such responses
observed as a consequence of stress exposure.
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Affiliation(s)
| | | | - Regina Helena Costa Queiroz
- Departamento de Análise Clínica - Toxicológica e Ciência de Alimentos, Faculdade de Ciências Farmacêuticas, USP, São Paulo, SP, Brasil
| | - Agnaldo Bruno Chies
- Departamento de Farmacologia, Instituto de Biociências, Universidade Estadual Paulista, São Paulo, SP, Brasil
| | - Sandra Cordellini
- Departamento de Farmacologia, Instituto de Biociências, Universidade Estadual Paulista, São Paulo, SP, Brasil
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Da Silva AL, Ruginsk SG, Uchoa ET, Crestani CC, Scopinho AA, Correa FMA, De Martinis BS, Elias LLK, Resstel LB, Antunes-Rodrigues J. Time-course of neuroendocrine changes and its correlation with hypertension induced by ethanol consumption. Alcohol Alcohol 2013; 48:495-504. [PMID: 23733506 DOI: 10.1093/alcalc/agt040] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
UNLABELLED Ethanol (ETOH) consumption has been associated with endocrine and autonomic changes, including the development of hypertension. However, the sequence of pathophysiological events underlying the emergence of this effect is poorly understood. AIMS This study aimed to establish a time-course correlation between neuroendocrine and cardiovascular changes contributing to the development of hypertension following ETOH consumption. METHODS Male adult Wistar rats were subjected to the intake of increasing ETOH concentrations in their drinking water (first week: 5%, second week: 10%, third and fourth weeks: 20% v/v). RESULTS ETOH consumption decreased plasma and urinary volumes, as well as body weight and fluid intake. Furthermore, plasma osmolality, plasma sodium and urinary osmolality were elevated in the ETOH-treated rats. ETOH intake also induced a progressive increase in the mean arterial pressure (MAP), without affecting heart rate. Initially, this increase in MAP was correlated with increased plasma concentrations of adrenaline and noradrenaline. After the second week of ETOH treatment, plasma catecholamines returned to basal levels, and incremental increases were observed in plasma concentrations of vasopressin (AVP) and angiotensin II (ANG II). Conversely, plasma oxytocin, atrial natriuretic peptide, prolactin and the hypothalamus-pituitary-adrenal axis components were not significantly altered by ETOH. CONCLUSIONS Taken together, these results suggest that increased sympathetic activity may contribute to the early increase in MAP observed in ETOH-treated rats. However, the maintenance of this effect may be predominantly regulated by the long-term increase in the secretion of other circulating factors, such as AVP and ANG II, the secretion of both hormones being stimulated by the ETOH-induced dehydration.
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Affiliation(s)
- Andreia Lopes Da Silva
- Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
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Hipólito UV, Rocha JT, Martins-Oliveira A, Tirapelli DPC, Jacob-Ferreira A, Batalhão ME, Tanus-Santos JE, Carnio EC, Cunha TM, Queiroz RH, Tirapelli CR. Chronic ethanol consumption reduces adrenomedullin-induced relaxation in the isolated rat aorta. Alcohol 2011; 45:805-14. [PMID: 21824741 DOI: 10.1016/j.alcohol.2011.06.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2011] [Revised: 06/14/2011] [Accepted: 06/24/2011] [Indexed: 12/28/2022]
Abstract
Adrenomedullin (AM) is a peptide that displays cardiovascular protective activity. We investigated the effects of chronic ethanol consumption on vascular reactivity to AM and the expression of AM system components in the rat aorta. Male Wistar rats were treated with ethanol (20% vol/vol) for 6 weeks. Vascular reactivity experiments were performed in the isolated rat aorta. Metalloproteinase-2 (MMP-2) levels were determined by gelatin zymography. Nitrite and nitrate generation was measured by chemiluminescence. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor (CRLR) and RAMP1, 2, and 3 (receptor-activity-modifying proteins) were assessed by western blot and quantitative real-time polymerase chain reaction, respectively. Ethanol intake reduced AM-induced relaxation in endothelium-intact rat aortas, whereas calcitonin gene-related peptide-, acetylcholine-, and sodium nitroprusside-induced relaxation were not affected by ethanol intake. N(G)-nitro-l-arginine-methyl-ester (l-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and tetraethylammonium reduced AM-induced relaxation in aortic rings from both control and ethanol-treated rats. Ethanol consumption did not alter basal levels of nitrate and nitrite, nor did it affect the expression of MMP-2 in the rat aorta. Ethanol consumption increased mRNA levels of pre-pro-AM and RAMP1. Protein levels of AM, CRLR, and RAMP1, 2, and 3 were not affected by ethanol consumption. The major findings of the present study are that ethanol consumption reduces the vascular relaxation induced by AM and changes the mRNA expression of the components of the AM system in the vasculature. This response could be one of the mechanisms by which ethanol predisposes individuals to vascular dysfunction and hypertension.
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Affiliation(s)
- Ulisses V Hipólito
- Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil
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Rocha JT, Hipólito UV, Martins-Oliveira A, Tirapelli DPC, Batalhão ME, Carnio EC, Queiroz RH, Coelho EB, Cunha TM, Tanus-Santos JE, Tirapelli CR. Ethanol consumption alters the expression and reactivity of adrenomedullin in the rat mesenteric arterial bed. Alcohol Alcohol 2011; 47:9-17. [PMID: 22021555 DOI: 10.1093/alcalc/agr141] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
AIMS Adrenomedullin (AM) is a peptide that displays cardiovascular protective activity. We investigated the effects of chronic ethanol consumption on arterial blood pressure, vascular reactivity to AM and the expression of AM system components in the rat mesenteric arterial bed (MAB). METHODS Male Wistar rats were treated with ethanol (20% vol/vol) for 6 weeks. Systolic, diastolic and mean arterial blood pressure were monitored in conscious rats. Vascular reactivity experiments were performed on isolated rat MAB. Matrix metalloproteinase-2 (MMP-2) levels were determined by gelatin zymography. Nitrite and nitrate generation were measured by chemiluminescence. Protein and mRNA levels of pre-pro-AM, CRLR (calcitonin receptor-like receptor) and RAMP1, 2 and 3 (receptor activity-modifying proteins) were assessed by western blot and quantitative real-time polymerase chain reaction, respectively. RESULTS Ethanol consumption induced hypertension and decreased the relaxation induced by AM and acetylcholine in endothelium-intact rat MAB. Phenylephrine-induced contraction was increased in endothelium-intact MAB from ethanol-treated rats. Ethanol consumption did not alter basal levels of nitrate and nitrite, nor did it affect the expression of MMP-2 or the net MMP activity in the rat MAB. Ethanol consumption increased mRNA levels of pre-pro-AM and protein levels of AM in the rat MAB. Finally, no differences in protein levels or mRNA of CRLR and RAMP1, 2 and 3 were observed after treatment with ethanol. CONCLUSION Our study demonstrates that ethanol consumption increases blood pressure and the expression of AM in the vasculature and reduces the relaxation induced by this peptide in the rat MAB.
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Affiliation(s)
- Juliana T Rocha
- College of Nursing of Ribeirão Preto, University of São Paulo, Brazil
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Purdie GL, Purdie DJ, Harrison AA. Raynaud's phenomenon in medical laboratory workers who work with solvents. J Rheumatol 2011; 38:1940-6. [PMID: 21677001 DOI: 10.3899/jrheum.101129] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To investigate whether there is an association between Raynaud's phenomenon (RP) and exposure to organic solvents in laboratory workers. METHODS Technicians, scientists, and laboratory assistants working in histology, cytology, and transfusion medicine were surveyed about their use of solvents, particularly xylene and toluene, and about symptoms of RP. There were 341 responses. OR for having worked with solvents were calculated with logistic regression adjusted for age and sex. RESULTS Laboratory workers who had worked with solvents had higher rates of severe RP, particularly those who had worked with xylene or toluene and either acetone (OR 8.8, 95% CI 1.9-41.1), or chlorinated solvents (OR 8.9, 95% CI 1.9-41.6), xylene or toluene and acetone compared to those who had worked with xylene or toluene but not acetone (OR 4.5, 95% CI 1.2-16.2), and similarly for chlorinated solvents (OR 4.5, 95% CI 1.2-16.3). RP symptoms occurring in the absence of cold exposure were more frequent for those who had worked with any solvent (OR 3.6, 95% CI 1.2-10.5) and just xylene or toluene (OR 2.8, 95% CI 1.1-7.3). Associations were also seen between increasing exposure to xylene or toluene and severe RP (OR 1.7, 95% CI 1.1-2.7, per 10 years) and with symptoms occurring in the absence of cold exposure (OR 1.7, 95% CI 1.2-2.5, per 10 years). CONCLUSION We found that exposure to solvents may be associated with the development of RP, supporting previous work indicating that solvent exposure may be an etiological factor in systemic sclerosis.
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Affiliation(s)
- Gordon L Purdie
- Department of Public Health, University of Otago Wellington, PO Box 7343, Wellington South, New Zealand.
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Husain K, Ferder L, Ansari RA, Lalla J. Chronic ethanol ingestion induces aortic inflammation/oxidative endothelial injury and hypertension in rats. Hum Exp Toxicol 2010; 30:930-9. [PMID: 20921064 DOI: 10.1177/0960327110384520] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The study aim was to investigate the relationship of chronic ethanol-induced inflammation leading to vascular endothelial injury and elevation of blood pressure (BP) in a rat model. Male Fisher rats were divided into two groups of six animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks and (2) 20% ethanol (4 g kg(-1), orally) daily for 12 weeks. The mean arterial blood pressure was recorded every week. The animals were anesthetized with pentobarbital after 12 weeks; thoracic aorta were isolated and analyzed for aortic reactivity response, inflammatory mediators, oxidant/antioxidant enzyme protein expression and endothelial nitric oxide-generating system. The results show that the mean BP was significantly elevated 12 weeks after ethanol ingestion. The increased BP was related to increased aortic inflammation (tumor necrosis factor [TNF]-α; nitric oxide synthase [iNOS], COX-2 and MCP-1 protein expression) and elevated angiotensin II levels in alcohol-treated group compared to control. Aortic Nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity, membrane and cytosolic subunits p22(phox) and p47(phox) expression and Mn-SOD activity and protein expression significantly increased, whereas nitric oxide (NO), endothelial NO synthase (eNOS), vascular endothelial growth factor (VEGF)-A and CuZn-SOD activity and protein expression significantly decreased in alcohol-treated group compared to control. The acetylcholine-mediated vasorelaxation response was depressed in the aorta of ethanol-treated rats compared to control. In conclusion, chronic ethanol-induced elevation in BP is related to increased aortic inflammation, elevated angiotensin II levels, induction of NADPH oxidase causing endothelial injury, depletion of CuZn-SOD, down-regulation of endothelial NO generating system and impaired vascular relaxation in rats.
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Affiliation(s)
- Kazim Husain
- Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, Ponce, PR, USA.
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Sönmez MF, Narin F, Balcioğlu E. Melatonin and Vitamin C Attenuates Alcohol-Induced Oxidative Stress in Aorta. Basic Clin Pharmacol Toxicol 2009; 105:410-5. [DOI: 10.1111/j.1742-7843.2009.00469.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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De Minicis S, Brenner DA. Oxidative stress in alcoholic liver disease: role of NADPH oxidase complex. J Gastroenterol Hepatol 2008; 23 Suppl 1:S98-103. [PMID: 18336675 DOI: 10.1111/j.1440-1746.2007.05277.x] [Citation(s) in RCA: 84] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Alcohol is a well-known risk factor for liver damage and is one of the major causes of liver disease worldwide. Chronic intake of alcohol, over a certain limit, inevitably leads to hepatic steatosis. If the injury persists, steatosis with concomitant tumor necrosis factor-alpha and other cytokines, progresses to steatohepatitis, fibrosis and finally cirrhosis. Among the multiple factors involved in the process of alcohol-induced liver injury, a crucial role is played by oxidative stress. Several mechanisms during ethanol metabolism result in reactive oxygen species (ROS) production. Although the main site of ethanol metabolism is hepatocytes, other mechanisms are involved in alcohol-induced liver injury. Specifically, in the ROS production activity, an important role is played by the NADPH oxidase complex. NADPH oxidase is expressed in hepatocytes, hepatic stellate cells and Kupffer cells in the liver. Studying NADPH oxidase gives new insights into alcohol-induced liver damage and provides new direction for future therapeutic strategies.
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Affiliation(s)
- Samuele De Minicis
- UCSD School of Medicine, Department of Medicine, La Jolla, California 92093-0602, USA
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