Evaluation of chronic treatment of 6-nitronoradrenaline in rats

• Grant number: 22/08022-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2022
• End date: January 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Gilberto Quirino dos Santos Junior
• 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

Endothelial cells modulate vascular reactivity through the release of mediators such as nitric oxide and endothelin. Current dogma is that catecholamines modulate vascular tone, chronotropism and cardiac inotropism through their release from adrenergic terminals, and by acting on alpha and beta adrenergic receptors. We identified through mass spectrometry endothelium-dependent basal release of dopamine in human vascular tissues (umbilical arteries and vessels, structures that are known to have no nerve terminals), indicating that dopamine of endothelial origin has the potential to modulate vascular reactivity. We also identified the release of a new catecholamine, 6-nitrodopamine (6ND), from human tissues. 6-ND has several actions on the cardiovascular system. It is a potent vasodilator, acting through the antagonism of D2-like dopamine receptors, and 100 times more potent than noradrenaline and adrenaline and 10,000 times more potent than dopamine as a chronotropic agent. At the moment, we do not know whether this action of 6-ND is due to itself, or to a possible metabolism of 6-nitroadrenaline (6-NN) and 6-nitroadrenaline (6-NA). The objective of this work is to understand the physiological and pathophysiological role of 6-NA, through chronic treatment in rats. (AU)

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; GUIMARAES, RENAN ARTHUR BOSIO; OLIVEIRA, DENIS LIMA; LIMA, ANTONIO TIAGO; QUIRINO, GILBERTO; STOCCO, GABRIEL AUGUSTO DE OLIVEIRA; URAMOTO, EDSON HIROSHI SALGADO; FREGONESI, ADRIANO; ANTUNES, EDSON; DE NUCCI, GILBERTO. Alpha₁-adrenergic blockers selectively antagonize the contractions induced by 6-nitrodopamine in the human vas deferens. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. 397, n. 5, p. 12-pg., 2023-11-01. (17/15175-1, 19/16805-4, 21/13593-6, 22/08022-2, 21/14414-8)

QUIRINO JUNIOR, GILBERTO; BRITTO-JUNIOR, JOSE; MAGALHAES, TAINAH BABADOPULOS; CAMPOS, RAFAEL; NYAMKONDIWA, KUDZAI L.; KLUGH, KAMERON L.; PETERSON, LARRYN W.; CORVINO, ANGELA; SPARACO, ROSA; FRECENTESE, FRANCESCO; et al. Measurement of 6-cyanodopamine, 6-nitrodopa, 6-nitrodopamine and 6-nitroadrenaline by LC-MS/MS in Krebs-Henseleit solution. Assessment of basal release from rabbit isolated right atrium and ventricles. BIOMEDICAL CHROMATOGRAPHY, v. N/A, p. 14-pg., 2023-07-10. (21/14414-8, 22/08022-2, 19/16805-4, 22/08232-7)