GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation
Abstract Background Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal sympathetic nerve activity that negates the diuresis and natriuresis as a negative feedback mechanism in normal rats. Ho...
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doaj-bf4dd5329bf046f08c53757d81618fdb2020-11-25T02:40:33ZengBMCCardiovascular Diabetology1475-28402020-05-0119111610.1186/s12933-020-01029-0GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervationKenichi Katsurada0Shyam S. Nandi1Hong Zheng2Xuefei Liu3Neeru M. Sharma4Kaushik P. Patel5Department of Cellular and Integrative Physiology, University of Nebraska Medical CenterDepartment of Cellular and Integrative Physiology, University of Nebraska Medical CenterDivision of Basic Biomedical Sciences, Sanford School of Medicine of the University of South DakotaDivision of Basic Biomedical Sciences, Sanford School of Medicine of the University of South DakotaDepartment of Cellular and Integrative Physiology, University of Nebraska Medical CenterDepartment of Cellular and Integrative Physiology, University of Nebraska Medical CenterAbstract Background Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal sympathetic nerve activity that negates the diuresis and natriuresis as a negative feedback mechanism in normal rats. However, renal effects of GLP-1 in heart failure (HF) has not been elucidated. The present study was designed to assess GLP-1-induced diuresis and natriuresis in rats with HF and its interactions with renal nerve activity. Methods HF was induced in rats by coronary artery ligation. The direct recording of afferent renal nerve activity (ARNA) with intrapelvic injection of GLP-1 and total renal sympathetic nerve activity (RSNA) with intravenous infusion of GLP-1 were performed. GLP-1 receptor expression in renal pelvis, densely innervated by afferent renal nerve, was assessed by real-time PCR and western blot analysis. In separate group of rats after coronary artery ligation selective afferent renal denervation (A-RDN) was performed by periaxonal application of capsaicin, then intravenous infusion of GLP-1-induced diuresis and natriuresis were evaluated. Results In HF, compared to sham-operated control; (1) response of increase in ARNA to intrapelvic injection of GLP-1 was enhanced (3.7 ± 0.4 vs. 2.0 ± 0.4 µV s), (2) GLP-1 receptor expression was increased in renal pelvis, (3) response of increase in RSNA to intravenous infusion of GLP-1 was enhanced (132 ± 30% vs. 70 ± 16% of the baseline level), and (4) diuretic and natriuretic responses to intravenous infusion of GLP-1 were blunted (urine flow 53.4 ± 4.3 vs. 78.6 ± 4.4 µl/min/gkw, sodium excretion 7.4 ± 0.8 vs. 10.9 ± 1.0 µEq/min/gkw). A-RDN induced significant increases in diuretic and natriuretic responses to GLP-1 in HF (urine flow 96.0 ± 1.9 vs. 53.4 ± 4.3 µl/min/gkw, sodium excretion 13.6 ± 1.4 vs. 7.4 ± 0.8 µEq/min/gkw). Conclusions The excessive activation of neural circuitry involving afferent and efferent renal nerves suppresses diuretic and natriuretic responses to GLP-1 in HF. These pathophysiological responses to GLP-1 might be involved in the interaction between incretin-based medicines and established HF condition. RDN restores diuretic and natriuretic effects of GLP-1 and thus has potential beneficial therapeutic implication for diabetic HF patients.http://link.springer.com/article/10.1186/s12933-020-01029-0Glucagon-like peptide-1Renal afferentSympathetic nerve activitySodium and water homeostasisHeart failure |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kenichi Katsurada Shyam S. Nandi Hong Zheng Xuefei Liu Neeru M. Sharma Kaushik P. Patel |
spellingShingle |
Kenichi Katsurada Shyam S. Nandi Hong Zheng Xuefei Liu Neeru M. Sharma Kaushik P. Patel GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation Cardiovascular Diabetology Glucagon-like peptide-1 Renal afferent Sympathetic nerve activity Sodium and water homeostasis Heart failure |
author_facet |
Kenichi Katsurada Shyam S. Nandi Hong Zheng Xuefei Liu Neeru M. Sharma Kaushik P. Patel |
author_sort |
Kenichi Katsurada |
title |
GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation |
title_short |
GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation |
title_full |
GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation |
title_fullStr |
GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation |
title_full_unstemmed |
GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation |
title_sort |
glp-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation |
publisher |
BMC |
series |
Cardiovascular Diabetology |
issn |
1475-2840 |
publishDate |
2020-05-01 |
description |
Abstract Background Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal sympathetic nerve activity that negates the diuresis and natriuresis as a negative feedback mechanism in normal rats. However, renal effects of GLP-1 in heart failure (HF) has not been elucidated. The present study was designed to assess GLP-1-induced diuresis and natriuresis in rats with HF and its interactions with renal nerve activity. Methods HF was induced in rats by coronary artery ligation. The direct recording of afferent renal nerve activity (ARNA) with intrapelvic injection of GLP-1 and total renal sympathetic nerve activity (RSNA) with intravenous infusion of GLP-1 were performed. GLP-1 receptor expression in renal pelvis, densely innervated by afferent renal nerve, was assessed by real-time PCR and western blot analysis. In separate group of rats after coronary artery ligation selective afferent renal denervation (A-RDN) was performed by periaxonal application of capsaicin, then intravenous infusion of GLP-1-induced diuresis and natriuresis were evaluated. Results In HF, compared to sham-operated control; (1) response of increase in ARNA to intrapelvic injection of GLP-1 was enhanced (3.7 ± 0.4 vs. 2.0 ± 0.4 µV s), (2) GLP-1 receptor expression was increased in renal pelvis, (3) response of increase in RSNA to intravenous infusion of GLP-1 was enhanced (132 ± 30% vs. 70 ± 16% of the baseline level), and (4) diuretic and natriuretic responses to intravenous infusion of GLP-1 were blunted (urine flow 53.4 ± 4.3 vs. 78.6 ± 4.4 µl/min/gkw, sodium excretion 7.4 ± 0.8 vs. 10.9 ± 1.0 µEq/min/gkw). A-RDN induced significant increases in diuretic and natriuretic responses to GLP-1 in HF (urine flow 96.0 ± 1.9 vs. 53.4 ± 4.3 µl/min/gkw, sodium excretion 13.6 ± 1.4 vs. 7.4 ± 0.8 µEq/min/gkw). Conclusions The excessive activation of neural circuitry involving afferent and efferent renal nerves suppresses diuretic and natriuretic responses to GLP-1 in HF. These pathophysiological responses to GLP-1 might be involved in the interaction between incretin-based medicines and established HF condition. RDN restores diuretic and natriuretic effects of GLP-1 and thus has potential beneficial therapeutic implication for diabetic HF patients. |
topic |
Glucagon-like peptide-1 Renal afferent Sympathetic nerve activity Sodium and water homeostasis Heart failure |
url |
http://link.springer.com/article/10.1186/s12933-020-01029-0 |
work_keys_str_mv |
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