Evaluation of the in vitro and in vivo cardiovascular effects of 6-nitrodopa in the rat

• Grant number: 24/12679-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Kashif Ali
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 19/16805-4 - Evaluation of the pathophysiological role of endothelial catecholamines, AP.TEM

Abstract

The autonomic nervous system is an important regulator of the cardiovascular system, with adrenergic and cholinergic innervations present in the heart. The endothelium is an organ capable of regulating vascular tone through the release of relaxing agents, such as nitric oxide and prostacyclin, or contractile agents, such as endothelins and angiotensin. Physiologically, this regulation also occurs through the release of catecholamines of neural origin. Studies on tissues isolated from reptiles have demonstrated that the endothelium is a source of catecholamines, as aortic contraction induced by electrical stimulation is abolished by adrenergic antagonists and removal of the endothelium. Recently, it was discovered that the endothelium releases dopamine and 6-nitrodopamine, non-neurogenic catecholamines that play a fundamental role in modulating the cardiovascular system. 6-Nitrodopa, a new catecholamine, was recently detected in isolated atria and ventricles of rabbits and is the main catecholamine circulating in rat plasma. However, it is not yet known whether 6-nitrodopa has any cardiovascular effects. Therefore, the objective of this project is to evaluate the in vitro and in vivo cardiovascular effects of this new nitrocatecholamine. To achieve this, we will use an in vitro pharmacological approach with the Langendorff technique, isolated rat atrium, arteries and veins of rats and pigs to investigate the mechanism of action of 6-nitrodopa, and an in vivo pharmacological approach through assays that evaluate the heart rate and mean arterial pressure in conscious and anesthetized rats. It is expected that the results obtained will provide significant information about the physiological and pathophysiological relevance of this nitrocatecholamine, expanding scientific knowledge about its cardiovascular effects. (AU)