Ang-(1-7)/Mas and ET-1/ETR cross-talk in vascular smooth muscle cells: implications in vascular dysfunction in hypertension

• Grant number: 18/11464-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 20, 2018
• End date: February 19, 2019
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Evelin Capellari Cárnio
• Grantee: Patrícia Passaglia
• Supervisor: Rhian Merry Touyz
• Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Glasgow, Scotland
• Associated to the scholarship: 14/22477-6 - Participation of angiotensin-(1-7) in the regulation of synthesis and release of vasopressin during endotoxemia, BP.DR

Abstract

Angiotensin (Ang)-(1-7) is a major component of the renin-angiotensin system and acts predominantly through G protein-coupled receptor (GPCR) Mas. Studies previously demonstrated that in endothelial cells, there is important cross-talk between Ang-(1-7)/Mas and the endothelin-1/ETBR system, which is vasoprotective. However, the importance of this cross talk between the Ang-(1-7)/Mas and endothelin-1 system in other vascular cell types, such as vascular smooth muscle cells (VSMCs), remains unknown. Then, the overall objective of this study is to determine whether there is cross-talk between the Ang-(1-7) and ET-1 systems and to evaluate whether MasR influences ETAR and ETBR signalling in VSMCs. We will also evaluate whether these systems are perturbed in hypertension, where endothelial function is impaired and where vascular contraction, inflammation and fibrosis are exaggerated, effects mediated by ET-1. Male wild-type and LinA3 mice will used for experimentation and VSMC derived from rat mesenteric arteries. VSMCs will be stimulated with ET-1, Ang-(1-7) and/or pre-incubated with an inhibitory peptide designed to disrupt the Mas/ETBR interaction. Responses related to contraction, inflammation, fibrosis and reactive oxygen species formation will be evaluated by real-time PCR, western blotting, measurement of intracellular free Ca2+ concentration, lucigenin-enhanced chemiluminescence assay, and myography to assess vascular function. Mean values ± SEM will be calculated for each experiment and statistical comparisons were made with 1-way ANOVA followed by Newman-Keuls test. P<0.05 will be considered statistically significant. (AU)