Participation of the cyclooxygenase enzyme (Cox) and of reactive species of oxygen (ROS) on angiotensin II-stimulated contractile response in rat aortas

• Grant number: 16/23235-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2017
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Lusiane Maria Bendhack
• Grantee: Jéssica Aparecida Pelegrin
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The vascular endothelium plays an important role on vascular tone by production of contractile and relaxing factors. The angiotensin II (AngIl) causes increasing of the blood pressure, endothelial dysfunction, vascular smooth muscle hypertrophy and induces the inflammatory and vasoactive substances production that perform an important role on the pathophysiology of cardiovascular diseases, such as hypertension, arteriosclerosis and cardiac insufficiency. Many authors demonstrated increasing of the reactive oxygen species (ROS) production due to the AT1 receptors activation by the AngIl. The main source of ROS in vascular cells is the enzyme NADPH oxidase (NOX), which activates the production of the contractile prostanoids by the greater activation of cyclooxygenase (COX). The aim of this work is to study the role of the ROS produced by the NOX and its interaction with the prostanoids produced by the COX in endothelial and vascular smooth muscle cells from rat aortas. Among the products of the COX, we will study the effects of the Thromboxane A2, which is responsible for the activation of the TP receptors, that cause vasoconstriction and platelet aggregation. The study will be performed in rat aortas with or without endothelium stimulated with AngII. The effect of inhibitors and antagonists will be evaluated on the contractile response stimulated by the AngIl and by the ROS production. In order to evaluate the effects of the AngIl on the NOX activation and the ROS production, the superoxide anion scavenger (Tiron) and the NOX inhibitor (Apocynin) will be used. In order to evaluate the effects of the AngIl on the COX activation, the non-selective COX inhibitor (COX-1 and COX-2) ibuprofen as well as the TP receptor antagonist (SQ29548) will also be used. This will allow us to evaluate if the AngIl-stimulated contractile response due to the AT1 receptors activation in rat aortas is modulated by NOX and/or COX products. We will also evaluate if these responses depend on the NOX and COX expressed on the vascular endothelium. (AU)