Changes in Purinergic Signaling in the Carotid Body of Heart Failure Rats.

• Grant number: 25/01691-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2025
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Davi José de Almeida Moraes
• Grantee: Valéria Cabral Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06886-7 - Role of purinergic receptors in the carotid body in heart failure, AP.JP2

Abstract

The activation of carotid bodies (CBs) promotes the release of ATP, an excitatory neurotransmitter that elicits cardiovascular, sympatho-excitatory and expiratory responses in rodents. In congestive heart failure (CHF), chronic CBs activation contributes to autonomic dysregulation and disease progression by increasing sympathetic activity and respiratory disorders. This sympathetic hyperactivity is associated with reduced quality of life and increased mortality. Previous studies have demonstrated that blocking P2X3 purinergic receptors in CBs suppressed their spontaneous and aberrant activity and normalized the sympathetic activity in rats with CHF. In this context, the hypothesis of the Master's Project is that ATP bioavailability is increased in the CBs of rats with CHF. This increase may be attributed to greater ATP release by CBs or to the amplification of paracrine signaling mediated by ATP and connexins. Furthermore, changes in the expression or activity of ectonucleotidases may elevate ATP bioavailability in CBs. This study aims to measure the ATP release and ectonucleotidases expression in the CBs of sham and CHF rats, as well as to analyze the expression of P2Y2 purinergic receptors and connexins. To achieve this, CHF will be induced by myocardial infarction, a surgical procedure in which rats will undergo ligation of the left coronary artery. CBs will be isolated for the analysis of mRNA expression, ATP release, and protein content. Understanding ATP and how to reduce its concentration in CBs may provide a pathway to a therapeutic approach with minimal side effects for CHF.