Characterization of the 6-ND receptor through in vitro evaluation of nitrated analogues of propranolol and atenolol without positive chronotropic effects induced by 6-nitrodopamine, dopamine, noradrenaline and adrenaline.

• Grant number: 23/16075-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2024
• End date: June 30, 2028
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Denis Lima Oliveira
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

It is classically accepted that the cardiovascular system is essentially modulated by the activity of the autonomic nervous system, with the sympathetic system being responsible for the positive chronotropic and inotropic effects. This view was called into question with the discovery that catecholamines are also produced by endothelium. 6-Nitrodopamine (6-ND) has a more powerful positive chronotropic and inotropic effect than the classic catecholamines dopamine, norepinephrine and adrenaline. Its origin in the cardiovascular system is not neurogenic, and its effects are antagonized by b1 adrenergic receptor antagonists, at concentrations that do not affect the chronotropic and inotropic effects caused by classical catecholamines, indicating the existence of a possible receptor for 6-ND.The objective of this work is to evaluate the effect of nitrated derivatives of propranolol and atenolol on the positive chronotropic and inotropic effects induced by catecholamines in isolated rat right atrium and isolated rat heart (Langendorff), respectively. The aim would be to characterize the mechanism of action of these nitrated derivatives, with the aim of eventually using them to identify the 6-ND receptor. Another objective is to verify whether, in the case of nitrated derivatives of atenolol, they occur in vivo, in patients who are taking atenolol chronically.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BRITTO-JUNIOR, JOSE; LIMA, ANTONIO TIAGO; OLIVEIRA, DENIS LIMA; MARIANO, FERNANDA, V; DE SOUZA, VALERIA BARBOSA; SCHENKA, ANDRE ALMEIDA; PETERSON, LARRYN W.; SLOT, MARIA SKOVBJERG; FJORD, REBECCA; WANG, TOBIAS; et al. 6-Cyanodopamine as an endogenous modulator of heart chronotropism and inotropism. Life Sciences, v. 366, p. 13-pg., 2025-02-24. (21/13726-6, 19/16805-4, 21/13593-6, 17/15175-1, 23/16075-1, 23/04217-6, 21/14414-8)