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Differential effects of sodium chloride and monosodium glutamate on kidney of adult and aging mice. Sci Rep 2021; 11:481. [PMID: 33436880 PMCID: PMC7804302 DOI: 10.1038/s41598-020-80048-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 12/11/2020] [Indexed: 02/06/2023] Open
Abstract
Monosodium Glutamate (MSG) is used as flavour enhancer, with potential beneficial effects due to its nutritional value. Given the decline in kidney functions during aging, we investigated the impact of MSG voluntary intake on the kidney of male mice, aged 6 or 18 months. For 2 months, they freely consumed water (control group), sodium chloride (0.3% NaCl) or MSG (1% MSG) in addition to standard diet. Young animals consuming sodium chloride presented signs of proteinuria, hyperfiltration, enhanced expression and excretion of Aquaporin 2 and initial degenerative reactions suggestive of fibrosis, while MSG-consuming mice were similar to controls. In old mice, aging-related effects including proteinuria and increased renal corpuscle volume were observed in all groups. At an advanced age, MSG caused no adverse effects on the kidney compared to controls, despite the presence of a sodium moiety, similar to sodium chloride. These data show that prolonged MSG intake in mice has less impact on kidney compared to sodium chloride, that already in young animals induced some effects on kidney, possibly related to hypertension.
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Armstrong LE, Muñoz CX, Armstrong EM. Distinguishing Low and High Water Consumers-A Paradigm of Disease Risk. Nutrients 2020; 12:E858. [PMID: 32210168 PMCID: PMC7146321 DOI: 10.3390/nu12030858] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 03/18/2020] [Accepted: 03/20/2020] [Indexed: 12/31/2022] Open
Abstract
A long-standing body of clinical observations associates low 24-h total water intake (TWI = water + beverages + food moisture) with acute renal disorders such as kidney stones and urinary tract infections. These findings prompted observational studies and experimental interventions comparing habitual low volume (LOW) and high volume (HIGH) drinkers. Investigators have learned that the TWI of LOW and HIGH differ by 1-2 L·d-1, their hematological values (e.g., plasma osmolality, plasma sodium) are similar and lie within the laboratory reference ranges of healthy adults and both groups appear to successfully maintain water-electrolyte homeostasis. However, LOW differs from HIGH in urinary biomarkers (e.g., reduced urine volume and increased osmolality or specific gravity), as well as higher plasma concentrations of arginine vasopressin (AVP) and cortisol. Further, evidence suggests that both a low daily TWI and/or elevated plasma AVP influence the development and progression of metabolic syndrome, diabetes, obesity, chronic kidney disease, hypertension and cardiovascular disease. Based on these studies, we propose a theory of increased disease risk in LOW that involves chronic release of fluid-electrolyte (i.e., AVP) and stress (i.e., cortisol) hormones. This narrative review describes small but important differences between LOW and HIGH, advises future investigations and provides practical dietary recommendations for LOW that are intended to decrease their risk of chronic diseases.
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Affiliation(s)
- Lawrence E. Armstrong
- Professor Emeritus, Human Performance Laboratory and Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA
| | - Colleen X. Muñoz
- Assistant Professor, Department of Health Sciences, University of Hartford, West Hartford, CT 06117, USA;
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Li L, Sun FH, Huang WYJ, Wong SHS. Effects of whey protein in carbohydrate-electrolyte drinks on post-exercise rehydration. Eur J Sport Sci 2018; 18:685-694. [PMID: 29490577 DOI: 10.1080/17461391.2018.1442499] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
The purpose of this study was to examine the effects of different amounts of whey protein in carbohydrate-electrolyte (CE) drinks on post-exercise rehydration. Ten males completed 5 trials in a randomised cross-over design. A 4-h recovery was applied after a 60-min run at 65% VO2peak in each trial. During recovery, the participants ingested a high-carbohydrate CE drink (CE-H), a low-carbohydrate CE drink (CE-L), a high-whey-protein (33 g·L-1) CE drink (CW-H), a medium-whey-protein (22 g·L-1) CE drink (CW-M) or a low-whey-protein (15 g·L-1) CE drink (CW-L) in a volume equivalent to 150% of their body mass (BM) loss. The drinks were provided in six equal boluses and consumed by the participants within 150 min in each trial. After exercise, a BM loss of 2.15% ± 0.05% was achieved. Urine production was less in the CW-M and CW-H trials during recovery, which induced a greater fluid retention in the CW-M (51.0% ± 5.7%) and CW-H (55.4% ± 3.8%) trials than in any other trial (p < .05). The plasma albumin content was higher in the CW-H trial than in the CE-H and CE-L trials at 2 h (p < .05) and 3 h (p < .01) during recovery. The aldosterone concentration was lower in the CE-H trial than in the CW-M and CW-H trials after recovery (p < .05). It is concluded that the rehydration was improved when whey protein was co-ingested with CE drinks during a 4-h recovery after a 60-min run. However, this additive effect was only observed when whey protein concentration was at least 22 g·L-1 in the current study.
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Affiliation(s)
- Liang Li
- a Youth Sport Research & Development Center , China Institute of Sport Science , Beijing , People's Republic of China
| | - Feng-Hua Sun
- b Department of Health and Physical Education , The Education University of Hong Kong , Tai Po , New Territories , Hong Kong
| | - Wendy Ya-Jun Huang
- c Department of Physical Education , Hong Kong Baptist University , Kowloon Tong , Kowloon , Hong Kong
| | - Stephen Heung-Sang Wong
- d Department of Sports Science and Physical Education , The Chinese University of Hong Kong , Shatin , New Territories , Hong Kong
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Busk TM, Bendtsen F, Poulsen JH, Clemmesen JO, Larsen FS, Goetze JP, Iversen JS, Jensen MT, Møgelvang R, Pedersen EB, Bech JN, Møller S. Transjugular intrahepatic portosystemic shunt: impact on systemic hemodynamics and renal and cardiac function in patients with cirrhosis. Am J Physiol Gastrointest Liver Physiol 2018; 314:G275-G286. [PMID: 29074483 DOI: 10.1152/ajpgi.00094.2017] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension and possibly increases central blood volume (CBV). Moreover, renal function often improves; however, its effects on cardiac function are unclear. The aims of our study were to examine the effects of TIPS on hemodynamics and renal and cardiac function in patients with cirrhosis. In 25 cirrhotic patients, we analyzed systemic, cardiac, and splanchnic hemodynamics by catheterization of the liver veins and right heart chambers before and 1 wk after TIPS. Additionally, we measured renal and cardiac markers and performed advanced echocardiography before, 1 wk after, and 4 mo after TIPS. CBV increased significantly after TIPS (+4.6%, P < 0.05). Cardiac output (CO) increased (+15.3%, P < 0.005) due to an increase in stroke volume (SV) (+11.1%, P < 0.005), whereas heart rate (HR) was initially unchanged. Cardiopulmonary pressures increased after TIPS, whereas copeptin, a marker of vasopressin, decreased (-18%, P < 0.005) and proatrial natriuretic peptide increased (+52%, P < 0.0005) 1 wk after TIPS and returned to baseline 4 mo after TIPS. Plasma neutrophil gelatinase-associated lipocalin, renin, aldosterone, and serum creatinine decreased after TIPS (-36%, P < 0.005; -65%, P < 0.05; -90%, P < 0.005; and -13%, P < 0.005, respectively). Echocardiography revealed subtle changes in cardiac function after TIPS, although these were within the normal range. TIPS increases CBV by increasing CO and SV, whereas HR is initially unaltered. These results indicate an inability to increase the heart rate in response to a hemodynamic challenge that only partially increases CBV after TIPS. These changes, however, are sufficient for improving renal function. NEW & NOTEWORTHY For the first time, we have combined advanced techniques to study the integrated effects of transjugular intrahepatic portosystemic shunt (TIPS) in cirrhosis. We showed that TIPS increases central blood volume (CBV) through improved cardiac inotropy. Advanced echocardiography demonstrated that myocardial function was unaffected by the dramatic increase in preload after TIPS. Finally, renal function improved due to the increase in CBV. Recognition of these physiological changes significantly contributes to our clinical understanding of TIPS.
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Affiliation(s)
- Troels M Busk
- Department of Clinical Physiology and Nuclear Medicine, Centre of Functional Imaging and Research, Copenhagen University Hospital Hvidovre , Copenhagen , Denmark
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre , Copenhagen , Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre , Copenhagen , Denmark
| | - Jørgen H Poulsen
- Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre, Copenhagen , Denmark
| | - Jens O Clemmesen
- Department of Hepatology, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Fin S Larsen
- Department of Hepatology, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Jens P Goetze
- Department of Clinical Biochemistry, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Jens S Iversen
- Department of Nephrology, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Magnus T Jensen
- Department of Cardiology, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Rasmus Møgelvang
- Department of Cardiology, Copenhagen University Rigshospitalet , Copenhagen , Denmark
| | - Erling B Pedersen
- University Clinic of Nephrology and Hypertension, Department of Medical Research and Medicine, Holstebro Hospital and Aarhus University , Aarhus , Denmark
| | - Jesper N Bech
- University Clinic of Nephrology and Hypertension, Department of Medical Research and Medicine, Holstebro Hospital and Aarhus University , Aarhus , Denmark
| | - Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Centre of Functional Imaging and Research, Copenhagen University Hospital Hvidovre , Copenhagen , Denmark
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Pourafshar N, Pourafshar S, Soleimani M. Urine Ammonium, Metabolic Acidosis and Progression of Chronic Kidney Disease. Nephron Clin Pract 2017; 138:222-228. [PMID: 29050011 DOI: 10.1159/000481892] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 09/28/2017] [Indexed: 11/19/2022] Open
Abstract
The metabolism of a typical Western diet generates 50-100 mEq of acid (H+) per day, which must be excreted in the urine for the systemic acid-base to remain in balance. The 2 major mechanisms that are responsible for the renal elimination of daily acid under normal conditions are ammonium (NH4+) excretion and titratable acidity. In the presence of systemic acidosis, ammonium excretion is intensified and becomes the crucial mechanism for the elimination of acid. The impairment in NH4+ excretion is therefore associated with reduced acid excretion, which causes excess accumulation of acid in the body and consequently results in metabolic acidosis. Chronic kidney disease (CKD) is associated with the impairment in acid excretion and precipitation of metabolic acidosis, which has an adverse effect on the progression of CKD. Recent studies suggest that the progressive decline in renal ammonium excretion in CKD is an important determinant of the ensuing systemic metabolic acidosis and is an independent factor for predicting the worsening of kidney function. While these studies have been primarily performed in hypertensive individuals with CKD, a closer look at renal NH4+ excretion in non-hypertensive individuals with CKD is warranted to ascertain its role in the progression of kidney disease.
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Affiliation(s)
- Negiin Pourafshar
- Department of Medicine at University of Virginia, Charlottesville, Virginia, USA
| | - Shirin Pourafshar
- Department of Medicine at University of Virginia, Charlottesville, Virginia, USA
| | - Manoocher Soleimani
- Department of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.,Department of Medicine Services, Veterans Medical Center, Cincinnati, Ohio, USA
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Jensen JM, Mose FH, Kulik AEO, Bech JN, Fenton RA, Pedersen EB. Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment. World J Nephrol 2015; 4:423-437. [PMID: 26167467 PMCID: PMC4491934 DOI: 10.5527/wjn.v4.i3.423] [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: 11/13/2014] [Revised: 03/08/2015] [Accepted: 04/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To quantify changes in urinary excretion of aquaporin2 water channels (u-AQP2), the sodium-potassium-chloride co-transporter (u-NKCC2) and the epithelial sodium channels (u-ENaC) during treatment with bendroflumethiazide (BFTZ), amiloride and placebo.
METHODS: In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fluid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.25 mg or placebo twice a day for 4.5 d before each examination day. On the examination day, glomerular filtration rate was measured by the constant infusion clearance technique with 51Cr-EDTA as reference substance. To estimate the changes in water transport via AQP2 and sodium transport via NKCC2 and ENaC, u-NKCC2, the gamma fraction of ENaC (u-ENaCγ), and u-AQP2 were measured at baseline and after infusion with 3% hypertonic saline. U-NKCC2, u-ENaCγ, u-AQP2 and plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin II (p-ANG II) and aldosterone (p-Aldo) were measured, by radioimmunoassay. Central blood pressure was estimated by applanation tonometry and body fluid volumes were estimated by bio-impedance spectroscopy. General linear model with repeated measures or related samples Friedman’s two-way analysis was used to compare differences. Post hoc Bonferroni correction was used for multiple comparisons of post infusion periods to baseline within each treatment group.
RESULTS: At baseline there were no differences in u-NKCC2, u-ENaCγ and u-AQP2. PRC, p-Ang II and p-Aldo were increased during active treatments (P < 0.001). After hypertonic saline, u-NKCC2 increased during amiloride (6% ± 34%; P = 0.081) and increased significantly during placebo (17% ± 24%; P = 0.010). U-AQP2 increased significantly during amiloride (31% ± 22%; P < 0.001) and placebo (34% ± 27%; P < 0.001), while u-NKCC2 and u-AQP2 did not change significantly during BFTZ (-7% ± 28%; P = 0.257 and 5% ± 16%; P = 0.261). U- ENaCγ increased in all three groups (P < 0.050). PRC, AngII and p-Aldo decreased to the same extent, while AVP increased, but to a smaller degree during BFTZ (P = 0.048). cDBP decreased significantly during BFTZ (P < 0.001), but not during amiloride or placebo. There were no significant differences in body fluid volumes.
CONCLUSION: After hypertonic saline, u-NKCC2 and u-AQP2 increased during amiloride, but not during BFTZ. Lower p-AVP during BFTZ potentially caused less stimulation of NKCC2 and AQP2 and subsequent lower reabsorption of water and sodium.
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Li L, Wong SHS, Sun FH. Effects of protein addition to carbohydrate-electrolyte solutions on postexercise rehydration. J Exerc Sci Fit 2015. [PMID: 29541093 DOI: 10.1016/j.jesf.2014.11.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background/Objective This study aimed to examine the effects of the addition of whey or casein protein, the two major proteins in milk, to carbohydrate-electrolyte (CE) solutions on postexercise rehydration. Methods Ten young men aged 20.7 ± 1.4 years with an average VO2max of 60.7 mL/kg/min ran for 60 minutes at 65% VO2max on three occasions followed by 4 hours' recovery. During recovery, the participants consumed either CE solution with 66 g/L carbohydrate (CHO), or CE plus whey protein solution (CW trial, 44 g/L CHO, 22 g/L whey), or CE plus casein protein solution (CC trial, 44 g/L CHO, 22 g/L casein); the solutions were matched for energy and electrolyte content. Results The participants lost 2.36 ± 0.32% of their pre-exercise body weight after the exercise. Total urine output after recovery was greater in the CE and CC trials than CW trial (CE vs. CW vs. CC: 1184 ± 378 mL vs. 1005 ± 214 mL vs. 1256 ± 413 mL; p < 0.05). Fluid retention after ingestion of CW solution was greater than CE and CC solutions (CE vs. CW vs. CC: 46.9 ± 16.5% vs. 54.9 ± 9.2% vs. 45.8 ± 17.3%; p < 0.05). Lower urine specific gravity and urine osmolality were observed by the end of recovery in the CE trial compared with CW trial (p < 0.05). No difference was found in the changes in plasma volume in all trials. Conclusion These results suggest that during the 4 hours' recovery after a 60-minute run, the CW solution was more effective for rehydration compared with the CE or CC solution.
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Affiliation(s)
- Liang Li
- Department of Sports Science and Physical Education, The Chinese University of Hong Kong, Shatin, Hong Kong.,Youth Sport Research and Development Center, China Institute of Sport Science, Beijing, China
| | - Stephen Heung-Sang Wong
- Department of Sports Science and Physical Education, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Feng-Hua Sun
- Department of Health and Physical Education, The Hong Kong Institute of Education, Tai Po, Hong Kong
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Mose FH, Larsen T, Jensen JM, Hansen AB, Bech JN, Pedersen EB. Effects of atorvastatin on systemic and renal NO dependency in patients with non-diabetic stage II-III chronic kidney disease. Br J Clin Pharmacol 2014; 78:789-799. [PMID: 24697877 PMCID: PMC4239973 DOI: 10.1111/bcp.12390] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Accepted: 03/25/2014] [Indexed: 12/20/2022] Open
Abstract
AIMS Clinical trials suggest that statins have beneficial effects on the cardiovascular system independent from their cholesterol lowering properties. In patients with chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-N(G) -monomethyl arginine (L-NMMA) as an inhibitor of NO production. METHODS In a randomized, placebo-controlled, crossover study patients were treated with atorvastatin for 5 days with standardized diet and fluid intake. Glomerular filtration reate (GFR), fractional excretions of sodium (FENa ), urinary excretion of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ ), vasoactive hormones (renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide) and central blood pressure (BP) estimated by applanation tonometry were measured before and after systemic administration of the NO inhibitor L-NMMA. RESULTS Atorvastatin caused a significant reduction in U-ENaCγ , but sodium excretion, C H 2 O , FENa and u-AQP2 were not changed by atorvastatin. L-NMMA reduced renal effect variables, including GFR, FENa and u-ENaCγ and increased brachial BP and central BP to a similar extent during both treatments. Vasoactive hormones were changed in the same way by L-NMMA during atorvastatin and placebo treatment. CONCLUSION During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, the data do not support that atorvastatin changes nitric oxide availability in patients with mild nephropathy. The reduced u-ENaC may reflect changes in sodium absorption in the nephron induced by atorvastatin.
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Affiliation(s)
- Frank Holden Mose
- Department of Medical Research, University Clinic in Hypertension and Nephrology, Holstebro HospitalHolstebro, Denmark
| | - Thomas Larsen
- Department of Medical Research, University Clinic in Hypertension and Nephrology, Holstebro HospitalHolstebro, Denmark
| | - Janni Majgaard Jensen
- Department of Medical Research, University Clinic in Hypertension and Nephrology, Holstebro HospitalHolstebro, Denmark
| | | | - Jesper Nørgaard Bech
- Department of Medical Research, University Clinic in Hypertension and Nephrology, Holstebro HospitalHolstebro, Denmark
- Department of Medicine, Holstebro Hospital and University of AarhusHolstebro, Denmark
| | - Erling Bjerregaard Pedersen
- Department of Medical Research, University Clinic in Hypertension and Nephrology, Holstebro HospitalHolstebro, Denmark
- Department of Medicine, Holstebro Hospital and University of AarhusHolstebro, Denmark
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Jensen JM, Mose FH, Kulik AEO, Bech JN, Fenton RA, Pedersen EB. Abnormal urinary excretion of NKCC2 and AQP2 in response to hypertonic saline in chronic kidney disease: an intervention study in patients with chronic kidney disease and healthy controls. BMC Nephrol 2014; 15:101. [PMID: 24970686 PMCID: PMC4094915 DOI: 10.1186/1471-2369-15-101] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Accepted: 06/11/2014] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Renal handling of sodium and water is abnormal in chronic kidney disease (CKD). The aim of this study was to test the hypothesis that abnormal activity of the aquaporin-2 water channels (AQP2), the sodium-potassium-2chloride transporter (NKCC2) and/or the epithelial sodium channels (ENaC) contribute to this phenomenon. METHODS 23 patients with CKD and 24 healthy controls at baseline and after 3% saline infusion were compared. The following measurements were performed: urinary concentrations of AQP2 (u-AQP2), NKCC2 (u-NKCC2), ENaC (u-ENaCγ), glomerular filtration rate (GFR) estimated by 51Cr-EDTA clearance, free water clearance (CH2O), urinary output (UO), fractional excretion of sodium (FENa), plasma concentrations of AVP, renin (PRC), Angiotensin II (ANG II), Aldosterone (Aldo) and body fluid volumes. RESULTS At baseline, GFR was 34 ml/min in CKD patients and 89 ml/ml in controls. There were no significant differences in u-AQP2, u-NKCC2 or u-ENaCγ, but FENa, p-Aldo and p-AVP were higher in CKD patients than controls. In response to hypertonic saline, patients with CKD had an attenuated decrease in CH2O and UO. A greater increase in U-AQP2 was observed in CKD patients compared to controls. Furthermore, u-NKCC2 increased in CKD patients, whereas u-NKCC2 decreased in controls. Body fluid volumes did not significantly differ. CONCLUSIONS In response to hypertonic saline, u-NKCC2 increased, suggesting an increased sodium reabsorption via NKCC2 in patients with CKD. U-AQP2 increased more in CKD patients, despite an attenuated decrease in CH2O. Thus, though high levels of p-AVP and p-Aldo, the kidneys can only partly compensate and counteract acute volume expansion due to a defective tubular response. TRIAL REGISTRATION Clinical trial no: NCT01623661. Date of trial registration: 18.06.2012.
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Affiliation(s)
- Janni M Jensen
- Department of Medical Research, Holstebro Hospital, University Clinic in Nephrology and Hypertension, Laegaardvej 12, 7500 Holstebro, Denmark
- Regional Hospital Jutland West and Aarhus University, Aarhus, Denmark
| | - Frank H Mose
- Department of Medical Research, Holstebro Hospital, University Clinic in Nephrology and Hypertension, Laegaardvej 12, 7500 Holstebro, Denmark
- Regional Hospital Jutland West and Aarhus University, Aarhus, Denmark
| | - Anna-Ewa O Kulik
- Department of Medical Research, Holstebro Hospital, University Clinic in Nephrology and Hypertension, Laegaardvej 12, 7500 Holstebro, Denmark
- Regional Hospital Jutland West and Aarhus University, Aarhus, Denmark
| | - Jesper N Bech
- Department of Medical Research, Holstebro Hospital, University Clinic in Nephrology and Hypertension, Laegaardvej 12, 7500 Holstebro, Denmark
- Regional Hospital Jutland West and Aarhus University, Aarhus, Denmark
| | - Robert A Fenton
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Erling B Pedersen
- Department of Medical Research, Holstebro Hospital, University Clinic in Nephrology and Hypertension, Laegaardvej 12, 7500 Holstebro, Denmark
- Regional Hospital Jutland West and Aarhus University, Aarhus, Denmark
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Al Therwani S, Mose FH, Jensen JM, Bech JN, Pedersen EB. Effect of vasopressin antagonism on renal handling of sodium and water and central and brachial blood pressure during inhibition of the nitric oxide system in healthy subjects. BMC Nephrol 2014; 15:100. [PMID: 24965902 PMCID: PMC4079642 DOI: 10.1186/1471-2369-15-100] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 06/19/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water excretion. We wanted to test the hypotheses that tolvaptan changes both renal handling of water and sodium and systemic hemodynamics during basal conditions and during nitric oxide (NO)-inhibition with L-NG-monomethyl-arginine (L-NMMA). METHODS Nineteen healthy subjects were enrolled in a randomized, placebo-controlled, double-blind, crossover study of two examination days. Tolvaptan 15 mg or placebo was given in the morning. L-NMMA was given as a bolus followed by continuous infusion during 60 minutes. We measured urine output(UO), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary aquaporin-2 channels (u-AQP2) and epithelial sodium channels (u-ENaCγ), plasma vasopressin (p-AVP), central and brachial blood pressure(cBP, bBP). RESULTS During baseline conditions, tolvaptan caused a significant increase in UO, CH2O and p-AVP, and FENa was unchanged. During L-NMMA infusion, UO and CH2O decreased more pronounced after tolvaptan than after placebo (-54 vs.-42% and -34 vs.-9% respectively). U-AQP2 decreased during both treatments, whereas u-ENaCγ decreased after placebo and increased after tolvaptan. CBP and bBP were unchanged. CONCLUSION During baseline conditions, tolvaptan increased renal water excretion. During NO-inhibition, the more pronounced reduction in renal water excretion after tolvaptan indicates that NO promotes water excretion in the principal cells, at least partly, via an AVP-dependent mechanism. The lack of decrease in u-AQP2 by tolvaptan could be explained by a counteracting effect of increased plasma vasopressin. The antagonizing effect of NO-inhibition on u-ENaC suggests that NO interferes with the transport via ENaC by an AVP-dependent mechanism.
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Affiliation(s)
- Safa Al Therwani
- University Clinic in Nephrology and Hypertension, Department of Medical Research, Holstebro Hospital and Aarhus University, Hospital Unit Jutland West, Laegaardvej 12, 7500 Holstebro, Denmark
| | - Frank Holden Mose
- University Clinic in Nephrology and Hypertension, Department of Medical Research, Holstebro Hospital and Aarhus University, Hospital Unit Jutland West, Laegaardvej 12, 7500 Holstebro, Denmark
| | - Janni Majgaard Jensen
- University Clinic in Nephrology and Hypertension, Department of Medical Research, Holstebro Hospital and Aarhus University, Hospital Unit Jutland West, Laegaardvej 12, 7500 Holstebro, Denmark
| | - Jesper Nørgaard Bech
- University Clinic in Nephrology and Hypertension, Department of Medical Research, Holstebro Hospital and Aarhus University, Hospital Unit Jutland West, Laegaardvej 12, 7500 Holstebro, Denmark
| | - Erling Bjerregaard Pedersen
- University Clinic in Nephrology and Hypertension, Department of Medical Research, Holstebro Hospital and Aarhus University, Hospital Unit Jutland West, Laegaardvej 12, 7500 Holstebro, Denmark
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Jensen JM, Mose FH, Bech JN, Nielsen S, Pedersen EB. Effect of volume expansion with hypertonic- and isotonic saline and isotonic glucose on sodium and water transport in the principal cells in the kidney. BMC Nephrol 2013; 14:202. [PMID: 24067081 PMCID: PMC3849534 DOI: 10.1186/1471-2369-14-202] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Accepted: 09/23/2013] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The renal distal nephron plays an important role in the maintenance of sodium balance, extra cellular volume and blood pressure. The degree of water transport, via aquaporin2 water channels (AQP2), and sodium transport, via epithelial sodium channels (ENaC) in renal collecting duct principal cells are reflected by the level of urinary excretion of AQP2 (u-AQP2) and the γ-fraction of ENaC (u-ENaCγ). The effects of an acute intravenous volume load with isotonic saline, hypertonic saline and glucose on u-AQP2, u-ENaCγ and underlying mechanisms have never been studied in a randomized, placebo-controlled trial in healthy humans. METHODS We studied the effects of 0.9% saline (23 ml/kg), 3% saline (7 ml/kg) and 5% glucose (23 ml/kg) on u-AQP2 and u-ENaCγ, fractional sodium excretion (FENa), free water clearance (CH2O), and plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (ANG II) and aldosterone (Aldo) in a randomized, crossover study of 23 healthy subjects, who consumed a standardized diet, regarding calories, sodium and fluid for 4 days before each examination day. RESULTS After isotonic saline infusion, u-AQP2 increased (27%). CH2O and u-ENaCγ were unchanged, whereas FENa increased (123%). After hypertonic saline infusion, there was an increase in u-AQP2 (25%), u-ENaCγ (19%) and FENa (96%), whereas CH2O decreased (-153%). After isotonic glucose infusion, there was a decrease in u-AQP2 (-16%), ENaCγ (-10%) and FENa (-44%) whereas CH2O increased (164%). AVP remained unchanged after isotonic saline and glucose, but increased after hypertonic saline (139%). PRC, AngII and p-Aldo decreased after isotonic and hypertonic saline infusion, but not after glucose infusion. CONCLUSIONS Volume expansion with 3% and 0.9% saline increased u-AQP2, while isotonic glucose decreased u-AQP2. Infusion of hypertonic saline increased u-ENaCγ, whereas u-ENaCγ was not significantly changed after isotonic saline and tended to decrease after glucose. Thus, the transport of water and sodium is changed both via the aquaporin 2 water channels and the epithelial sodium channels during all three types of volume expansion to regulate and maintain water- and sodium homeostasis in the body. TRIAL REGISTRATION Clinical Trial no: NCT01414088.
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Affiliation(s)
- Janni M Jensen
- Department of Medical Research, Holstebro Hospital, Laegaardvej 12, Holstebro 7500, Denmark
- Aarhus University, Aarhus, Denmark
| | - Frank H Mose
- Department of Medical Research, Holstebro Hospital, Laegaardvej 12, Holstebro 7500, Denmark
- Aarhus University, Aarhus, Denmark
| | - Jesper N Bech
- Department of Medical Research, Holstebro Hospital, Laegaardvej 12, Holstebro 7500, Denmark
- Aarhus University, Aarhus, Denmark
| | - Soren Nielsen
- Water and Salt Research Centre, Aarhus University, Aarhus, Denmark
| | - Erling B Pedersen
- Department of Medical Research, Holstebro Hospital, Laegaardvej 12, Holstebro 7500, Denmark
- Aarhus University, Aarhus, Denmark
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Matthesen SK, Larsen T, Vase H, Lauridsen TG, Jensen JM, Pedersen EB. Effect of amiloride and spironolactone on renal tubular function and central blood pressure in patients with arterial hypertension during baseline conditions and after furosemide: a double-blinded, randomized, placebo-controlled crossover trial. Clin Exp Hypertens 2012; 35:313-324. [PMID: 22966789 DOI: 10.3109/10641963.2012.721843] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
This study demonstrates that the increased potassium content in the body seems to change both the blood pressure and renal tubular function. We wanted to test the hypotheses that amiloride and spironolactone induced potassium retention reduces ambulatory blood pressure (ABP) and central blood pressure (CBP) during baseline conditions and after furosemide and that the tubular transport via the epithelial sodium channels (ENaCs) and aquaporin-2 (AQP2) water channels was increased by furosemide in arterial hypertension. Each of three 28-day treatment periods (placebo, amiloride, and spironolactone) was completed by a 4-day period with standardized diet regarding calories and sodium and water intake. At the end of each period, we measured pulse wave velocity (PWV), central systolic blood pressure (CSBP), central diastolic blood pressure (CDBP), glomerular filtration rate (GFR), free water clearance (CH2O), fractional excretion of sodium (FENa) and potassium (FEK), urinary excretion of AQP2 (u-AQP2), urinary excretion of γ-fraction of the ENaC (u-ENaCγ), and plasma concentrations of renin (PRC), angiotensin II (p-Ang II), and aldosterone (p-Aldo) at baseline conditions and after furosemide bolus. Ambulatory blood pressure and CBP were significantly lowered by amiloride and spironolactone. During 24-hour urine collection and at baseline, GFR, CH2O, FENa, FEK, u-AQP2 and u-ENaCγ were the same. After furosemide, CH2O, FENa, FEK, u-AQP2, u-ENaCγ, PRC, p-Ang II, p-Aldo, PWV and CDBP increased after all treatments. However, during amiloride treatment, FEK increased to a larger extent than after spironolactone and during placebo after furosemide, and CSBP was not significantly reduced. The increases in water and sodium absorption via AQP2 and ENaC after furosemide most likely are compensatory phenomena to antagonize water and sodium depletion. Amiloride is less effective than spironolactone to reduce renal potassium excretion.
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Affiliation(s)
- Solveig K Matthesen
- Departments of Medical Research and Medicine, Holstebro Hospital and University of Aarhus, Laegaardvej 12,Holstebro, Denmark.
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Matthesen SK, Larsen T, Lauridsen TG, Vase H, Gjørup PH, Nykjær KM, Nielsen S, Pedersen EB. Effect of amiloride and spironolactone on renal tubular function, ambulatory blood pressure, and pulse wave velocity in healthy participants in a double-blinded, randomized, placebo-controlled, crossover trial. Clin Exp Hypertens 2012; 34:588-600. [PMID: 22591021 DOI: 10.3109/10641963.2012.681730] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
We wanted to test the hypothesis that treatment with amiloride or spironolactone reduced ambulatory (ABP) and central blood pressure (CBP) and that tubular transport via ENaCγ and AQP2 was increased after furosemide treatment. During baseline conditions, there were no differences in ABP, CBP, renal tubular function, or plasma concentrations of vasoactive hormones. After furosemide treatment, an increase in CBP, CH(2)o, FE(Na), FE(K), u-AQP2/min, u-ENaCγ/min, PRC, p-Ang II, and p-Aldo was observed. The increases in water and sodium absorption via AQP2 and ENaC after furosemide treatment most likely are compensatory phenomena to antagonize water and sodium depletion.
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Affiliation(s)
- Solveig Klok Matthesen
- Department of Medical Research, Holstebro Hospital and University of Aarhus, Holstebro, Denmark.
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Graffe CC, Bech JN, Lauridsen TG, Pedersen EB. Urinary excretion of AQP2 and ENaC in autosomal dominant polycystic kidney disease during basal conditions and after a hypertonic saline infusion. Am J Physiol Renal Physiol 2012; 302:F917-F927. [PMID: 22262484 DOI: 10.1152/ajprenal.00616.2011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Renal handling of sodium and water is abnormal in chronic kidney diseases. To study the function and regulation of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in autosomal dominant polycystic kidney disease (ADPKD), we measured urinary excretion of AQP2 (u-AQP2), the β-subunit of ENaC (u-ENaC(β)), cAMP (u-cAMP), and prostaglandin E(2) (u-PGE(2)); free water clearance (C(H2O)); fractional sodium excretion (FE(Na)); and plasma vasopressin (p-AVP), renin (p-Renin), angiotensin II (p-ANG II), aldosterone (p-Aldo), and atrial and brain natriuretic peptide (p-ANP, p-BNP) in patients with ADPKD and healthy controls during 24-h urine collection and after hypertonic saline infusion during high sodium intake (HS; 300 mmol sodium/day) and low sodium intake (LS; 30 mmol sodium/day). No difference in u-AQP2, u-ENaC(β), u-cAMP, u-PGE(2), C(H2O), and vasoactive hormones was found between patients and controls at baseline, but during HS the patients had higher FE(Na). The saline caused higher increases in FE(Na) in patients than controls during LS, but the changes in u-ENaC(β), p-Aldo, p-ANP, p-BNP, p-Renin, and p-ANG II were similar. Higher increases in u-AQP2 and p-AVP were seen in patients during both diets. In conclusion, u-AQP2 and u-ENaC(β) were comparable in patients with ADPKD and controls at baseline. In ADPKD, the larger increase in u-AQP2 and p-AVP in response to saline could reflect an abnormal water absorption in the distal nephron. During LS, the larger increase in FE(Na) in response to saline could reflect a defective renal sodium retaining capacity in ADPKD, unrelated to changes in u-ENaC(β).
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Graffe CC, Bech JN, Lauridsen TG, Vase H, Pedersen EB. Abnormal increase in urinary aquaporin-2 excretion in response to hypertonic saline in essential hypertension. BMC Nephrol 2012; 13:15. [PMID: 22452789 PMCID: PMC3386017 DOI: 10.1186/1471-2369-13-15] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2011] [Accepted: 03/27/2012] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Dysregulation of the expression/shuttling of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in renal collecting duct principal cells has been found in animal models of hypertension. We tested whether a similar dysregulation exists in essential hypertension. METHODS We measured urinary excretion of AQP2 and ENaC β-subunit corrected for creatinine (u-AQP2(CR), u-ENaC(β-CR)), prostaglandin E2 (u-PGE2) and cyclic AMP (u-cAMP), fractional sodium excretion (FE(Na)), free water clearance (C(H2O)), as well as plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), and atrial and brain natriuretic peptide (ANP, BNP) in 21 patients with essential hypertension and 20 normotensive controls during 24-h urine collection (baseline), and after hypertonic saline infusion on a 4-day high sodium (HS) diet (300 mmol sodium/day) and a 4-day low sodium (LS) diet (30 mmol sodium/day). RESULTS At baseline, no differences in u-AQP2(CR) or u-ENaC(β-CR) were measured between patients and controls. U-AQP2(CR) increased significantly more after saline in patients than controls, whereas u-ENaC(β-CR) increased similarly. The saline caused exaggerated natriuretic increases in patients during HS intake. Neither baseline levels of u-PGE2, u-cAMP, AVP, PRC, Ang II, Aldo, ANP, and BNP nor changes after saline could explain the abnormal u-AQP2(CR) response. CONCLUSIONS No differences were found in u-AQP2(CR) and u-ENaC(β-CR) between patients and controls at baseline. However, in response to saline, u-AQP2(CR) was abnormally increased in patients, whereas the u-ENaC(β-CR) response was normal. The mechanism behind the abnormal AQP2 regulation is not clarified, but it does not seem to be AVP-dependent. Clinicaltrial.gov identifier: NCT00345124.
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Affiliation(s)
| | - Jesper Nørgaard Bech
- Department of Medical Research, Holstebro Hospital, Laegaardvej 12, 7500 Holstebro, Denmark
- Department of Medicine, Holstebro Hospital, Holstebro, Denmark
- University of Aarhus, Aarhus, Denmark
| | - Thomas Guldager Lauridsen
- Department of Medical Research, Holstebro Hospital, Laegaardvej 12, 7500 Holstebro, Denmark
- Department of Medicine, Holstebro Hospital, Holstebro, Denmark
| | - Henrik Vase
- Department of Medical Research, Holstebro Hospital, Laegaardvej 12, 7500 Holstebro, Denmark
| | - Erling Bjerregaard Pedersen
- Department of Medical Research, Holstebro Hospital, Laegaardvej 12, 7500 Holstebro, Denmark
- Department of Medicine, Holstebro Hospital, Holstebro, Denmark
- University of Aarhus, Aarhus, Denmark
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Matthesen SK, Larsen T, Vase H, Lauridsen TG, Pedersen EB. Effect of potassium supplementation on renal tubular function, ambulatory blood pressure and pulse wave velocity in healthy humans. Scand J Clin Lab Invest 2012; 72:78-86. [PMID: 22149452 DOI: 10.3109/00365513.2011.635216] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Potassium is the main intracellular cation, which contributes to keeping the intracellular membrane potential slightly negative and elicits contraction of smooth, skeletal and cardiac muscle. A change in potassium intake modifies both cardiovascular and renal tubular function. The purpose of the trial was to investigate the effect of dietary potassium supplementation, 100 mmol daily in a randomized, placebo-controlled, crossover trial of healthy participants during two periods of 28 days duration. The participants (N = 21) received a diet that was standardized regarding energy requirement, and sodium and water intake. METHODS 24-hour ambulatory blood pressure (ABP) and applanation tonometry were used to assess blood pressure, pulse wave velocity (PWV), augmentation index (AIx) and central blood pressure (CBP). Immunoassays were used for measurements of plasma concentrations of vasoactive hormones: renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP), vasopressin (AVP), pro-brain natriuretic peptide (pro-BNP),endothelin (Endo), urinary excretions of aquaporin 2 (AQP2), cyclic AMP (cAMP), and the β-fraction of the epithelial sodium channel (ENaC(ß)). RESULTS AQP2 excretion increased during potassium supplementation, and free water clearance fell. The changes in urinary potassium excretion and urinary AQP2 excretion were significantly and positively correlated. Aldo increased. GFR, u-ENaC- β, PRC, Ang II, ANP, BNP, Endo, blood pressure and AI were not significantly changed by potassium supplementation, whereas PWV increased slightly. CONCLUSIONS Potassium supplementation changed renal tubular function and increased water absorption in the distal part of the nephron. In spite of an increase in aldosterone in plasma, blood pressure remained unchanged after potassium supplementation.
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Affiliation(s)
- Solveig K Matthesen
- Department of Medical Research, Holstebro Regional Hospital, Laegaardvej 12, 7500 Holstebro, Denmark.
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Graffe CC, Bech JN, Pedersen EB. Effect of high and low sodium intake on urinary aquaporin-2 excretion in healthy humans. Am J Physiol Renal Physiol 2012; 302:F264-F275. [PMID: 21993890 DOI: 10.1152/ajprenal.00442.2010] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The degree of water transport via aquaporin-2 (AQP2) water channels in renal collecting duct principal cells is reflected by the level of the urinary excretion of AQP2 (u-AQP2). In rats, the AQP2 expression varies with sodium intake. In humans, the effect of sodium intake on u-AQP2 and the underlying mechanisms have not previously been studied. We measured the effect of 4 days of high sodium (HS) intake (300 mmol sodium/day; 17.5 g salt/day) and 4 days of low sodium (LS) intake (30 mmol sodium/day; 1.8 g salt/day) on u-AQP2, fractional sodium excretion (FE(Na)), free water clearance (C(H2O)), urinary excretion of PGE(2) (u-PGE(2)) and cAMP (u-cAMP), and plasma concentrations of vasopressin (AVP), renin (PRC), ANG II, aldosterone (Aldo), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in a randomized, crossover study of 21 healthy subjects, during 24-h urine collection and after hypertonic saline infusion. The 24-h urinary sodium excretion was significantly higher during HS intake (213 vs. 41 mmol/24 h). ANP and BNP were significantly lower and PRC, ANG II, and Aldo were significantly higher during LS intake. AVP, u-cAMP, and u-PGE(2) were similar during HS and LS intake, but u-AQP2 was significantly higher during HS intake. The increases in AVP and u-AQP2 in response to hypertonic saline infusion were similar during HS and LS intake. In conclusion, u-AQP2 was increased during HS intake, indicating that water transport via AQP2 was increased. The effect was mediated by an unknown AVP-independent mechanism.
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Krag A, Pedersen EB, Møller S, Bendtsen F. Effects of the vasopressin agonist terlipressin on plasma cAMP and ENaC excretion in the urine in patients with cirrhosis and water retention. Scand J Clin Lab Invest 2011; 71:112-116. [PMID: 21080762 DOI: 10.3109/00365513.2010.537369] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Terlipressin is a vasopressin analogue used for its potent V1a effects in cirrhotic patients. Recent data suggest that terlipressin has affinity to renal V2 receptors and modulates Aquaporin 2 (AQP2) expression and free water clearance. Stimulation of renal V2 receptors may also affect sodium transport via the Epithelial Sodium Channel (ENaC). Furthermore, endothelial V2 receptors may indirectly affect proximal sodium handling by increasing plasma cAMP. METHODS We investigated 18 patients with cirrhosis and ascites before and after infusion of 2 mg of terlipressin. Plasma cAMP and urine AQP2 were measured and a newly developed radioimmunoassay was used to quantify ENaC in the urine. RESULTS Mean arterial blood pressure increased from 87 ± 15 to 105 ± 19 mmHg, p < 0.001 after terlipressin infusion and GFR increased from 52 ± 6 to 69 ± 9 mL/min, p < 0.01. Urine-ENaC in ng/mmol creatinine increased from 42 ± 6 to 50 ± 7 ng/mmol creatinine, p = 0.05. Urine sodium increased from 43 ± 8 to 62 ± 9 mmol/L, p < 0.01. Plasma cAMP was not affected by terlipressin, 106 (63-673) vs. 103.5 (69-774) pmol/mL, NS. The rise in ENaC excretion correlated with the rise in AQP2 excretion, r = 0.63, p < 0.01. There was a weak correlation between the change in MAP and the rise in AQP2 excretion (p < 0.05). CONCLUSIONS Increased ENaC excretion suggests increased abundance of ENaC and resultant increased distal sodium reabsorption. The V2 effects of terlipressin are insufficient to stimulate the endothelial V2 receptors since plasma cAMP is unaltered. Despite pronounced V1a and some V2 effects of terlipressin, additional effects on proximal sodium handling are therefore not likely.
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Affiliation(s)
- Aleksander Krag
- Department of Gastroenterology, Hvidovre University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark.
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