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Soares JÍ, da Silva TM, Castania JA, Reis UÁ, Roque LFM, Ribeiro AB, Salgado HC, Ribeiro AB. Electrical carotid sinus nerve stimulation attenuates experimental colitis induced by acetic acid in rats. Life Sci 2023; 335:122281. [PMID: 37984513 DOI: 10.1016/j.lfs.2023.122281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 11/14/2023] [Accepted: 11/17/2023] [Indexed: 11/22/2023]
Abstract
AIMS The carotid bodies are sensors that detect physiological signals and convey them to the central nervous system, where the stimuli are processed inducing reflexes through efferent pathways. Recent studies have demonstrated that electrical stimulation of the carotid sinus nerve (CSN) triggers the anti-inflammatory reflex under different conditions. However, whether this electrical stimulation attenuates colitis was never examined. This study aimed to evaluate if the electrical CSN stimulation attenuates the experimental colitis induced by intrarectal administration of acetic acid in rats. METHODS Electrodes were implanted around the CSN to stimulate the CSN, and a catheter was inserted into the left femoral artery to record the arterial pressure. The observation of hypotensive responses confirmed the effectiveness of the electrical CNS stimulation. This maneuver was followed by a 4 % acetic acid or saline administered intrarectally. After 24 h, colons were segmented into distal and proximal parts for macroscopy, histological and biochemical assessment. KEY FINDINGS As expected, the electrical CSN stimulation was effective in decreasing arterial pressure in saline and colitis rats. Moreover, electrical CSN stimulation effectively reduced colonic tissue lesions, colitis scores, and histopathologic parameters associated with colitis. In addition, the CSN stimulation also reduced the colonic mucosa pro-inflammatory cytokine interleukin-1 beta, and increased the anti-inflammatory interleukin-10, in rats submitted to colitis. SIGNIFICANCE These findings indicated that electrical CSN stimulation breaks the vicious cycle of local colon inflammation in colitis, which might contribute to its better outcome.
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Affiliation(s)
- Jefferson Ícaro Soares
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Thaís Marques da Silva
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Jaci Airton Castania
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | | | | | | | - Helio Cesar Salgado
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Aline Barbosa Ribeiro
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Barão de Mauá University Center, Ribeirão Preto, São Paulo, Brazil.
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2
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Zucker IH, Xia Z, Wang HJ. Potential Neuromodulation of the Cardio-Renal Syndrome. J Clin Med 2023; 12:803. [PMID: 36769450 PMCID: PMC9917464 DOI: 10.3390/jcm12030803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 01/16/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
The cardio-renal syndrome (CRS) type 2 is defined as a progressive loss of renal function following a primary insult to the myocardium that may be either acute or chronic but is accompanied by a decline in myocardial pump performance. The treatment of patients with CRS is difficult, and the disease often progresses to end-stage renal disease that is refractory to conventional therapy. While a good deal of information is known concerning renal injury in the CRS, less is understood about how reflex control of renal sympathetic nerve activity affects this syndrome. In this review, we provide insight into the role of the renal nerves, both from the afferent or sensory side and from the efferent side, in mediating renal dysfunction in CRS. We discuss how interventions such as renal denervation and abrogation of systemic reflexes may be used to alleviate renal dysfunction in the setting of chronic heart failure. We specifically focus on a novel cardiac sensory reflex that is sensitized in heart failure and activates the sympathetic nervous system, especially outflow to the kidney. This so-called Cardiac Sympathetic Afferent Reflex (CSAR) can be ablated using the potent neurotoxin resinferitoxin due to the high expression of Transient Receptor Potential Vanilloid 1 (TRPV1) receptors. Following ablation of the CSAR, several markers of renal dysfunction are reversed in the post-myocardial infarction heart failure state. This review puts forth the novel idea of neuromodulation at the cardiac level in the treatment of CRS Type 2.
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Affiliation(s)
- Irving H. Zucker
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Zhiqiu Xia
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Han-Jun Wang
- Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
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3
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Ribeiro AB, Brognara F, da Silva JF, Castania JA, Fernandes PG, Tostes RC, Salgado HC. Carotid sinus nerve stimulation attenuates alveolar bone loss and inflammation in experimental periodontitis. Sci Rep 2020; 10:19258. [PMID: 33159128 PMCID: PMC7648828 DOI: 10.1038/s41598-020-76194-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 10/23/2020] [Indexed: 12/12/2022] Open
Abstract
Baroreceptor and chemoreceptor reflexes modulate inflammatory responses. However, whether these reflexes attenuate periodontal diseases has been poorly examined. Thus, the present study determined the effects of electrical activation of the carotid sinus nerve (CSN) in rats with periodontitis. We hypothesized that activation of the baro and chemoreflexes attenuates alveolar bone loss and the associated inflammatory processes. Electrodes were implanted around the CSN, and bilateral ligation of the first mandibular molar was performed to, respectively, stimulate the CNS and induce periodontitis. The CSN was stimulated daily for 10 min, during nine days, in unanesthetized animals. On the eighth day, a catheter was inserted into the left femoral artery and, in the next day, the arterial pressure was recorded. Effectiveness of the CNS electrical stimulation was confirmed by hypotensive responses, which was followed by the collection of a blood sample, gingival tissue, and jaw. Long-term (9 days) electrical stimulation of the CSN attenuated bone loss and the histological damage around the first molar. In addition, the CSN stimulation also reduced the gingival and plasma pro-inflammatory cytokines induced by periodontitis. Thus, CSN stimulation has a protective effect on the development of periodontal disease mitigating alveolar bone loss and inflammatory processes.
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Affiliation(s)
- Aline Barbosa Ribeiro
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Avenida dos Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil
| | - Fernanda Brognara
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Avenida dos Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil
| | - Josiane Fernandes da Silva
- Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Jaci Airton Castania
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Avenida dos Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil
| | | | - Rita C Tostes
- Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil
| | - Helio Cesar Salgado
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Avenida dos Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil.
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4
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Fjordbakk CT, Miranda JA, Sokal D, Donegà M, Viscasillas J, Stathopoulou TR, Chew DJ, Perkins JD. Feasibility of kilohertz frequency alternating current neuromodulation of carotid sinus nerve activity in the pig. Sci Rep 2019; 9:18136. [PMID: 31792232 PMCID: PMC6889394 DOI: 10.1038/s41598-019-53566-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 11/04/2019] [Indexed: 12/19/2022] Open
Abstract
Recent research supports that over-activation of the carotid body plays a key role in metabolic diseases like type 2 diabetes. Supressing carotid body signalling through carotid sinus nerve (CSN) modulation may offer a therapeutic approach for treating such diseases. Here we anatomically and histologically characterised the CSN in the farm pig as a recommended path to translational medicine. We developed an acute in vivo porcine model to assess the application of kilohertz frequency alternating current (KHFAC) to the CSN of evoked chemo-afferent CSN responses. Our results demonstrate the feasibility of this approach in an acute setting, as KHFAC modulation was able to successfully, yet variably, block evoked chemo-afferent responses. The observed variability in blocking response is believed to reflect the complex and diverse anatomy of the porcine CSN, which closely resembles human anatomy, as well as the need for optimisation of electrodes and parameters for a human-sized nerve. Overall, these results demonstrate the feasibility of neuromodulation of the CSN in an anesthetised large animal model, and represent the first steps in driving KHFAC modulation towards clinical translation. Chronic recovery disease models will be required to assess safety and efficacy of this potential therapeutic modality for application in diabetes treatment.
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Affiliation(s)
- Cathrine T Fjordbakk
- The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK.,Cathrine T. Fjordbakk, Norwegian University of Life Sciences, Faculty of Veterinary Medicine, PO box 369, Sentrum, 0102, Oslo, Norway
| | - Jason A Miranda
- Galvani Bioelectronics, Translational Sciences, Stevenage, Herts, SG1 2NY, UK
| | - David Sokal
- Galvani Bioelectronics, Translational Sciences, Stevenage, Herts, SG1 2NY, UK
| | - Matteo Donegà
- Galvani Bioelectronics, Translational Sciences, Stevenage, Herts, SG1 2NY, UK
| | - Jaime Viscasillas
- The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK
| | | | - Daniel J Chew
- Galvani Bioelectronics, Translational Sciences, Stevenage, Herts, SG1 2NY, UK
| | - Justin D Perkins
- The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK.
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5
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Katayama PL, Castania JA, Fazan R, Salgado HC. Interaction between baroreflex and chemoreflex in the cardiorespiratory responses to stimulation of the carotid sinus/nerve in conscious rats. Auton Neurosci 2018; 216:17-24. [PMID: 30598121 DOI: 10.1016/j.autneu.2018.12.001] [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: 08/17/2018] [Revised: 11/30/2018] [Accepted: 12/01/2018] [Indexed: 11/29/2022]
Abstract
Electrical stimulation of the carotid baroreflex has been thoroughly investigated for treating drug-resistant hypertension in humans. However, a previous study from our laboratory, performed in conscious rats, has demonstrated that electrical stimulation of the carotid sinus/nerve (CS) activated both the carotid baroreflex as well as the carotid chemoreflex, resulting in hypotension. Additionally, we also demonstrated that the carotid chemoreceptor deactivation potentiated this hypotensive response. Therefore, to further investigate this carotid baroreflex/chemoreflex interaction, besides the hemodynamic responses, we evaluated the respiratory responses to the electrical stimulation of the CS in both intact (CONT) and carotid chemoreceptors deactivated (CHEMO-X) conscious rats. CONT rats showed increased ventilation in response to electrical stimulation of the CS as measured by the respiratory frequency (fR), tidal volume (VT) and minute ventilation (VE), suggesting a carotid chemoreflex activation. The carotid chemoreceptor deactivation abolished all respiratory responses to the electrical stimulation of the CS. Regarding the hemodynamic responses, the electrical stimulation of the CS caused hypotensive responses in CONT rats, which were potentiated by the carotid chemoreceptors deactivation. Heart rate (HR) responses did not differ between groups. In conclusion, the present study showed that the electrical stimulation of the CS, in conscious rats, activates both the carotid baroreflex and the carotid chemoreflex driving an increase in ventilation and a decrease in AP. These findings further contribute to our understanding of the electrical stimulation of CS.
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Affiliation(s)
- Pedro L Katayama
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Jaci A Castania
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Rubens Fazan
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Helio C Salgado
- Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
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6
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Safety profile of baroreflex activation therapy (NEO) in patients with resistant hypertension. J Hypertens 2018; 36:1762-1769. [DOI: 10.1097/hjh.0000000000001753] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Pourafshar N, Karimi A, Anderson RD, Alaei-Andabili SH, Kandzari DE. Renal Denervation: Past, Present, and Future. CARDIOVASCULAR INNOVATIONS AND APPLICATIONS 2016. [DOI: 10.15212/cvia.2016.0016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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8
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Kawamoto B, Shimizu S, Shimizu T, Higashi Y, Hikita K, Muraoka K, Honda M, Sejima T, Takenaka A, Saito M. Vesicovascular reflexes in the spontaneously hypertensive rat. Life Sci 2016; 144:202-7. [DOI: 10.1016/j.lfs.2015.12.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 11/01/2015] [Accepted: 12/02/2015] [Indexed: 11/25/2022]
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Doumas M, Douma S. Primary Aldosteronism: A Field on the Move. UPDATES IN HYPERTENSION AND CARDIOVASCULAR PROTECTION 2016. [DOI: 10.1007/978-3-319-34141-5_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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10
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11
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Silva EF, Sera CTN, Mourão AA, Lopes PR, Moreira MCS, Ferreira-Neto ML, Colombari DAS, Cravo SLD, Pedrino GR. Involvement of sinoaortic afferents in renal sympathoinhibition and vasodilation induced by acute hypernatremia. Clin Exp Pharmacol Physiol 2015; 42:1135-41. [DOI: 10.1111/1440-1681.12475] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 07/29/2015] [Accepted: 08/01/2015] [Indexed: 11/29/2022]
Affiliation(s)
- Elaine F Silva
- Centre for Neuroscience and Cardiovascular Research; Department of Physiological Sciences; Biological Sciences Institute; Federal University of Goiás; Goiânia Goiás Brazil
| | - Celisa TN Sera
- Department of Physiology; Federal University of São Paulo; São Paulo São Paulo Brazil
| | - Aline A Mourão
- Centre for Neuroscience and Cardiovascular Research; Department of Physiological Sciences; Biological Sciences Institute; Federal University of Goiás; Goiânia Goiás Brazil
| | - Paulo R Lopes
- Centre for Neuroscience and Cardiovascular Research; Department of Physiological Sciences; Biological Sciences Institute; Federal University of Goiás; Goiânia Goiás Brazil
| | - Marina CS Moreira
- Centre for Neuroscience and Cardiovascular Research; Department of Physiological Sciences; Biological Sciences Institute; Federal University of Goiás; Goiânia Goiás Brazil
| | - Marcos L Ferreira-Neto
- Laboratory of Experimental Physiology; Faculty of Physical Education; Federal University of Uberlândia; Uberlândia Minas Gerais Brazil
| | - Débora AS Colombari
- Department of Physiology and Pathology; School of Dentistry; São Paulo State University; Araraquara São Paulo Brazil
| | - Sérgio LD Cravo
- Department of Physiology; Federal University of São Paulo; São Paulo São Paulo Brazil
| | - Gustavo R Pedrino
- Centre for Neuroscience and Cardiovascular Research; Department of Physiological Sciences; Biological Sciences Institute; Federal University of Goiás; Goiânia Goiás Brazil
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12
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Wallbach M, Lehnig LY, Helms HJ, Schroer C, Müller GA, Wachter R, Koziolek MJ. Long-term effects of baroreflex activation therapy on glucose metabolism. Acta Diabetol 2015; 52:829-35. [PMID: 25539879 DOI: 10.1007/s00592-014-0679-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Accepted: 10/27/2014] [Indexed: 11/28/2022]
Abstract
AIMS Sympathetic overactivity is one critical factor associated with the development of arterial hypertension, impaired insulin secretion and resistance. Some antihypertensives exert beneficial effects on glucose metabolism, whereas others lead to an impairment of metabolic state with consecutive weight gain. In resistant hypertension, baroreflex activation therapy (BAT) reduces arterial blood pressure (BP) by inhibition of the sympathetic nervous system. The objective of this study was to evaluate whether BAT influences metabolic state in patients with resistant hypertension. METHODS Thirty patients with resistant hypertension (10 with known diabetes mellitus) were prospectively included into this study. Blood pressure, BMI, weight, fasting glucose, insulin, C-peptide, hemoglobin A1c, HOMA-IR, HOMA-β, ISQuickI, and glucose levels during oral glucose tolerance test were measured at baseline and 6 months after BAT activation. RESULTS Fasting glucose was significantly reduced after 6 months of BAT, whereas mean 2-h glucose levels during oral glucose tolerance test, fasting insulin levels, C-peptide levels, hemoglobin A1c, HOMA-IR, HOMA-β, ISQuickI, weight, and BMI remained unchanged. CONCLUSION Despite improvement in fasting glucose, BAT exerts neither sustained additional beneficial effects nor an impairment of metabolic state. Thus, chronic BAT might be an effective interventional method to reduce BP without metabolic disadvantages.
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Affiliation(s)
- Manuel Wallbach
- Department of Nephrology and Rheumatology, Georg-August-University Göttingen, Robert - Koch - Str. 40, 37075, Göttingen, Germany.
| | - Luca-Yves Lehnig
- Department of Nephrology and Rheumatology, Georg-August-University Göttingen, Robert - Koch - Str. 40, 37075, Göttingen, Germany
| | - Hans-Joachim Helms
- Department of Medical Statistics, Georg-August-University Göttingen, Göttingen, Germany
| | - Charlotte Schroer
- Department of Cardiology and Pneumology, Georg-August-University Göttingen, Göttingen, Germany
| | - Gerhard A Müller
- Department of Nephrology and Rheumatology, Georg-August-University Göttingen, Robert - Koch - Str. 40, 37075, Göttingen, Germany
| | - Rolf Wachter
- Department of Cardiology and Pneumology, Georg-August-University Göttingen, Göttingen, Germany
| | - Michael J Koziolek
- Department of Nephrology and Rheumatology, Georg-August-University Göttingen, Robert - Koch - Str. 40, 37075, Göttingen, Germany
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Fukuda K, Kanazawa H, Aizawa Y, Ardell JL, Shivkumar K. Cardiac innervation and sudden cardiac death. Circ Res 2015; 116:2005-19. [PMID: 26044253 PMCID: PMC4465108 DOI: 10.1161/circresaha.116.304679] [Citation(s) in RCA: 296] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Accepted: 12/11/2014] [Indexed: 12/14/2022]
Abstract
Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy, and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem, and higher centers), which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes to hours), and long term (days to years). This important neurovisceral/autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death. Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extracardiac neural remodeling has also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provide a rational mechanistic basis for the development of neuraxial therapies for preventing sudden cardiac death and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention.
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Affiliation(s)
- Keiichi Fukuda
- From the Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (K.F., H.K., Y.A.); and UCLA Cardiac Arrhythmia Center, Neurocardiology Research Center of Excellence (J.L.A., K.S.).
| | - Hideaki Kanazawa
- From the Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (K.F., H.K., Y.A.); and UCLA Cardiac Arrhythmia Center, Neurocardiology Research Center of Excellence (J.L.A., K.S.)
| | - Yoshiyasu Aizawa
- From the Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (K.F., H.K., Y.A.); and UCLA Cardiac Arrhythmia Center, Neurocardiology Research Center of Excellence (J.L.A., K.S.)
| | - Jeffrey L Ardell
- From the Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (K.F., H.K., Y.A.); and UCLA Cardiac Arrhythmia Center, Neurocardiology Research Center of Excellence (J.L.A., K.S.)
| | - Kalyanam Shivkumar
- From the Department of Cardiology, Keio University School of Medicine, Tokyo, Japan (K.F., H.K., Y.A.); and UCLA Cardiac Arrhythmia Center, Neurocardiology Research Center of Excellence (J.L.A., K.S.).
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Weber F, Anlauf M. Treatment resistant hypertension--investigation and conservative management. DEUTSCHES ARZTEBLATT INTERNATIONAL 2015; 111:425-31. [PMID: 25008301 DOI: 10.3238/arztebl.2014.0425] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 04/07/2014] [Accepted: 04/07/2014] [Indexed: 01/25/2023]
Abstract
BACKGROUND The introduction of invasive treatments, some of which are irreversible, for the entity called treatment-resistant hypertension (TRH) creates the need for a comprehensive discussion of the diagnostic evaluation that TRH requires and the available options for its conservative treatment. METHOD The pertinent literature is selectively reviewed in the light of the authors' longstanding clinical experience. RESULTS Our review of the literature suggests that the high prevalence of TRH in Germany (ca. 20%) can be nearly halved with the aid of more thorough diagnostic evaluation. Such an evaluation should include a review of the patient's antihypertensive drugs (adherence, daily dosing, concomitant medication), investigation for other vascular changes that might affect blood pressure measurement, and exclusion of white-coat hypertension, sleep apnea syndrome, and secondary rather than essential hypertension. As there have been no randomized trials of treatment for TRH, the physician confronted with such cases must devise treatments on the basis of observational data and pathophysiological reasoning (volume status considering renin levels, sympathetic blockade, vasodilatation). Such measures can presumably lower the number of truly treatment-resistant cases still further. CONCLUSION To save patients from preventable harm, patients should undergo a thorough diagnostic evaluation and-under close monitoring for side effects-conservative pharmacological and nonpharmacological treatments should be deployed before any invasive treatment is performed.
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Affiliation(s)
- Franz Weber
- St Walburga Hospital, Meschede, Private Practice at the Medical Care Center, Dialysis Center, Cuxhaven
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Charkoudian N, Wallin BG. Sympathetic neural activity to the cardiovascular system: integrator of systemic physiology and interindividual characteristics. Compr Physiol 2014; 4:825-50. [PMID: 24715570 DOI: 10.1002/cphy.c130038] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The sympathetic nervous system is a ubiquitous, integrating controller of myriad physiological functions. In the present article, we review the physiology of sympathetic neural control of cardiovascular function with a focus on integrative mechanisms in humans. Direct measurement of sympathetic neural activity (SNA) in humans can be accomplished using microneurography, most commonly performed in the peroneal (fibular) nerve. In humans, muscle SNA (MSNA) is composed of vasoconstrictor fibers; its best-recognized characteristic is its participation in transient, moment-to-moment control of arterial blood pressure via the arterial baroreflex. This property of MSNA contributes to its typical "bursting" pattern which is strongly linked to the cardiac cycle. Recent evidence suggests that sympathetic neural mechanisms and the baroreflex have important roles in the long term control of blood pressure as well. One of the striking characteristics of MSNA is its large interindividual variability. However, in young, normotensive humans, higher MSNA is not linked to higher blood pressure due to balancing influences of other cardiovascular variables. In men, an inverse relationship between MSNA and cardiac output is a major factor in this balance, whereas in women, beta-adrenergic vasodilation offsets the vasoconstrictor/pressor effects of higher MSNA. As people get older (and in people with hypertension) higher MSNA is more likely to be linked to higher blood pressure. Skin SNA (SSNA) can also be measured in humans, although interpretation of SSNA signals is complicated by multiple types of neurons involved (vasoconstrictor, vasodilator, sudomotor and pilomotor). In addition to blood pressure regulation, the sympathetic nervous system contributes to cardiovascular regulation during numerous other reflexes, including those involved in exercise, thermoregulation, chemoreflex regulation, and responses to mental stress.
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Affiliation(s)
- N Charkoudian
- U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts
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16
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Wallbach M, Lehnig LY, Schroer C, Hasenfuss G, Müller GA, Wachter R, Koziolek MJ. Impact of baroreflex activation therapy on renal function--a pilot study. Am J Nephrol 2014; 40:371-80. [PMID: 25358549 DOI: 10.1159/000368723] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Accepted: 09/27/2014] [Indexed: 01/06/2023]
Abstract
BACKGROUND/AIMS Resistant hypertension and chronic kidney disease (CKD) are interlinked via sympathetic overdrive. Baroreflex activation therapy (BAT) has been shown to chronically reduce blood pressure (BP) in patients with resistant hypertension. The effect of BAT on renal function in CKD patients with resistant hypertension has not been reported. The aim of this study was to investigate the effect of sympathetic inhibition on renal function in CKD patients. METHODS 23 CKD patients with resistant hypertension were prospectively treated with BAT. Analyses were performed before and 6 months after the start of BAT. The renal function was analyzed by creatinine, cystatin C, glomerular filtration rate (GFR), renin, aldosterone, fractioned and 24-hour sodium excretion and analyses of urine marker proteins. The purpose of the control group was to investigate the influence of treating patients in a center for hypertension and regression to the mean on investigated variables. RESULTS The office mean BP decreased from 116.9 ± 20.9 mm Hg to 104.2 ± 22.2 mm Hg (p < 0.01), while the number of prescribed antihypertensive classes decreased from 6.6 ± 1.6 to 6.1 ± 1.7 (p = 0.02). Proteinuria and albuminuria decreased from a median of 283.9 and 47.7 to 136.5 (p = 0.01) and 45.0 mg/g creatinine (p = 0.01) with pronounced effects in higher CKD stage III + IV compared to I + II (p < 0.01). CKD-EPI cystatin C equation improved from 53.6 ± 22.7 to 60.4 ± 26.1 ml/min (p = 0.02). While creatinine and GFR were impaired after a period of 6 months, no changes of proteinuria, albuminuria, or BP were obtained in control patients. CONCLUSION The data of this prospective trial demonstrate potential nephroprotective effects of BAT in therapy-resistant hypertension in CKD patients by a reduction of BP, proteinuria and moreover, a stabilization of estimated GFR.
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Affiliation(s)
- Manuel Wallbach
- Department of Nephrology and Rheumatology, Georg-August-University Goettingen, Germany
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Doumas M, Tsioufis C, Faselis C, Lazaridis A, Grassos H, Papademetriou V. Non-interventional management of resistant hypertension. World J Cardiol 2014; 6:1080-1090. [PMID: 25349652 PMCID: PMC4209434 DOI: 10.4330/wjc.v6.i10.1080] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Revised: 04/12/2014] [Accepted: 08/31/2014] [Indexed: 02/06/2023] Open
Abstract
Hypertension is one of the most popular fields of research in modern medicine due to its high prevalence and its major impact on cardiovascular risk and consequently on global health. Indeed, about one third of individuals worldwide has hypertension and is under increased long-term risk of myocardial infarction, stroke or cardiovascular death. On the other hand, resistant hypertension, the “uncontrollable” part of arterial hypertension despite appropriate therapy, comprises a much greater menace since long-standing, high levels of blood pressure along with concomitant debilitating entities such as chronic kidney disease and diabetes mellitus create a prominent high cardiovascular risk milieu. However, despite the alarming consequences, resistant hypertension and its effective management still have not received proper scientific attention. Aspects like the exact prevalence and prognosis are yet to be clarified. In an effort to manage patients with resistant hypertension appropriately, clinical doctors are still racking their brains in order to find the best therapeutic algorithm and surmount the substantial difficulties in controlling this clinical entity. This review aims to shed light on the effective management of resistant hypertension and provide practical recommendations for clinicians dealing with such patients.
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Drenjancevic I, Grizelj I, Harsanji-Drenjancevic I, Cavka A, Selthofer-Relatic K. The interplay between sympathetic overactivity, hypertension and heart rate variability (review, invited). ACTA ACUST UNITED AC 2014; 101:129-42. [PMID: 24901074 DOI: 10.1556/aphysiol.101.2014.2.1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The control of arterial pressure is a complex interaction of the long- and short-term influences of hormones, local vascular factors, and neural mechanisms. The autonomic nervous system and its sympathetic arm play important roles in the regulation of blood pressure, and overactivity of sympathetic nerves may have an important role in the development of hypertension and related cardiovascular disorders. The baroreceptor system opposes either increases or decreases in arterial pressure, and the primary purpose of the arterial baroreflex is to keep blood pressure close to a particular set point over a relatively short period of time. The ability of the baroreflex to powerfully buffer acute changes in arterial pressure is well established, but the role of the arterial baroreceptor reflex in long-term control of arterial pressure has been a topic of many debate and controversy for decades. The sympathetic nervous system and arterial baroreceptor reflex control of renal sympathetic nerve activity has been proposed to play a role in long-term control of arterial pressure. The aim of this paper has been to review the postulated role of sympathetic activation.
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Affiliation(s)
- Ines Drenjancevic
- University of Osijek Department of Physiology and Immunology, Faculty of Medicine J. Huttlera 4 31000 Osijek Croatia University of Pécs Pécs Hungary
| | - I Grizelj
- University of Osijek Department of Physiology and Immunology, Faculty of Medicine J. Huttlera 4 31000 Osijek Croatia
| | - I Harsanji-Drenjancevic
- Clinical Hospital Center Osijek Department of Anesthesiology, Reanimatology and Intensive Care Unit Osijek Croatia
| | - A Cavka
- University of Osijek Department of Physiology and Immunology, Faculty of Medicine J. Huttlera 4 31000 Osijek Croatia
| | - K Selthofer-Relatic
- Clinical Hospital Center Osijek Department of Cardiology, Clinic of Internal Medicine Osijek Croatia University of Osijek Department of Internal Medicine, Medical Ethic and History of Medicine, Faculty of Medicine Osijek Croatia
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Papademetriou V, Rashidi AA, Tsioufis C, Doumas M. Renal nerve ablation for resistant hypertension: how did we get here, present status, and future directions. Circulation 2014; 129:1440-51. [PMID: 24687645 DOI: 10.1161/circulationaha.113.005405] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Affiliation(s)
- Vasilios Papademetriou
- Department of Veterans Affairs and Georgetown University, Washington, DC (V.P., A.A.R.); Ippokration University Hospital, Athens, Greece (C.T.); Aristotle University of Thessaloniki, Thessaloniki, Greece (M.D.)
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