CARDIOVASCULAR EFFECT OF NEW ENDOGENOUS CATECHOLAMINES IN PIGS

• Grant number: 24/16759-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2025
• End date: April 30, 2030
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Guilherme Machado de Figueiredo Murari
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

A new set of endogenous mediators known as novel catecholamines has recently been described. The novel catecholamines include the group of 6-nitrocatecholamines (6-NCT) and derivatives with a cyanide group, such as 6-cyanodopamine (6-CD), constituting a broad family of catecholamine-derived mediators.The synthesis of 6-NCT occurs through the nitration of catecholamines by nitric oxide. 6-nitroepinephrine (6-NE) ¿¿and 6-nitrodopamine (6-ND) belong to this family. The endothelium of human umbilical cord vessels, the aorta of Chelonoidis carbonaria, the snake Panterophis guttatus and the marmoset (Callithrix spp) exhibit a basal release of 6-ND. The basal release of 6-ND, 6-NE and 6-CD in isolated rabbit atria and ventricles has also been described.In human umbilical cord blood vessels (HUC), 6-nitrodopamine acts as a D2-like antagonist, producing vasodilation. In isolated rat atria, 6-ND has a positive chronotropic effect 100 times more potent than dopamine (DA), norepinephrine (NE) and epinephrine (EP). In a Langendorff preparation with isolated rat heart, 6-ND demonstrates a potent positive inotropic effect.6-NE belongs to this family and has been shown to have several biological activities, such as inhibition of neuronal norepinephrine uptake, inhibition of neuronal nitric oxide synthase activity, inhibition of contractile capacity induced by vascular adrenoceptors and inhibition of COMT.In order to expand knowledge about these mediators in future clinical trials, it is important to understand the cardiovascular effects in animals in vivo. For this purpose, pigs are a widely used model due to the anatomical similarities between their cardiovascular system and that of humans.Therefore, this project aims to investigate the cardiovascular effects of new catecholamines in pigs by monitoring blood flow in various arterial beds, blood pressure, heart rate and cardiac output.