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GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation.
Cardiovasc Diabetol. 2020 05 08; 19(1):57.CD

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.

Authors+Show Affiliations

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE, 68198-5850, USA.Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE, 68198-5850, USA.Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, SD, USA.Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, SD, USA.Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE, 68198-5850, USA.Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE, 68198-5850, USA. kpatel@unmc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32384887

Citation

Katsurada, Kenichi, et al. "GLP-1 Mediated Diuresis and Natriuresis Are Blunted in Heart Failure and Restored By Selective Afferent Renal Denervation." Cardiovascular Diabetology, vol. 19, no. 1, 2020, p. 57.
Katsurada K, Nandi SS, Zheng H, et al. GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation. Cardiovasc Diabetol. 2020;19(1):57.
Katsurada, K., Nandi, S. S., Zheng, H., Liu, X., Sharma, N. M., & Patel, K. P. (2020). GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation. Cardiovascular Diabetology, 19(1), 57. https://doi.org/10.1186/s12933-020-01029-0
Katsurada K, et al. GLP-1 Mediated Diuresis and Natriuresis Are Blunted in Heart Failure and Restored By Selective Afferent Renal Denervation. Cardiovasc Diabetol. 2020 05 8;19(1):57. PubMed PMID: 32384887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation. AU - Katsurada,Kenichi, AU - Nandi,Shyam S, AU - Zheng,Hong, AU - Liu,Xuefei, AU - Sharma,Neeru M, AU - Patel,Kaushik P, Y1 - 2020/05/08/ PY - 2020/02/11/received PY - 2020/04/25/accepted PY - 2020/5/10/entrez PY - 2020/5/10/pubmed PY - 2020/5/10/medline KW - Glucagon-like peptide-1 KW - Heart failure KW - Renal afferent KW - Sodium and water homeostasis KW - Sympathetic nerve activity SP - 57 EP - 57 JF - Cardiovascular diabetology JO - Cardiovasc Diabetol VL - 19 IS - 1 N2 - 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. SN - 1475-2840 UR - https://www.unboundmedicine.com/medline/citation/32384887/GLP_1_mediated_diuresis_and_natriuresis_are_blunted_in_heart_failure_and_restored_by_selective_afferent_renal_denervation_ L2 - https://cardiab.biomedcentral.com/articles/10.1186/s12933-020-01029-0 DB - PRIME DP - Unbound Medicine ER -
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