Role of glucagon-like peptide-1 in the pathophysiology of hypertension

• Grant number: 17/13104-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2017
• End date: July 31, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Adriana Castello Costa Girardi
• Grantee: Flavia Leticia Martins
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 16/22140-7 - Molecular bases of renal tubular function and dysfunction, AP.TEM

Abstract

A large body of clinical and experimental evidence documents the importance of the kidney in defining the blood pressure (BP) set point and pathogenesis of hypertension. Body fluid volumes and Na+ balance are maintained by the renal regulation of a series of apical Na+ transporters located along the nephron. Changes in the number and/or intrinsic activity of these transporters affect Na+ reabsorption, body fluid volume and BP. Recent studies provide intriguing evidence that therapies aimed at normalizing blood glucose by mimicking the actions of the incretin hormone glucagon like peptide-1 (GLP-1) have beneficial effects by regulating renal Na+ transport and blood pressure. This project aims to test the hypothesis that the incretin hormone GLP-1 plays a role in the pathophysiology of hypertension. More specifically, (1) we will test the hypothesis that blocking the GLP-1R exacerbates hypertension in the SHR model at least in part by increasing expression, subcellular redistribution or alter the phosphorylation levels of sodium transporters in the renal tubule; (2) identify the mRNAs that are altered in the kidneys of SHRs in response to activation or antagonism of the GLP-1R receptor as compared with SHR treated with vehicle. As a result, we intend to identify the possible pathways (metabolic, anti-inflammatory, anti-apoptotic, antioxidant, etc.) that are altered by the GLP-1 receptor (GLP-1R) in the hypertensive rat kidney and that may be involved in maintaining high blood pressure levels in this experimental model; (3) test the hypothesis that the bioavailability and/or synthesis/ secretion of GLP-1 is impaired in SHRs. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MARTINS, Flavia Leticia. Long-term blockade of glucagon-like peptide-1 receptor increases systolic blood pressure levels in both hypertensive and normotensive rats. 2019. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.