Evaluation of the action of nitro-catecholamines in the cardiovascular system

• Grant number: 21/14414-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2022
• End date: November 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: José Britto Júnior
• 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
• Associated scholarship(s): 23/14557-9 - The transduction mechanism(s) employed by 6-nitrodopamine and 6-cyanodopamine in human platelets and cultured cell lines, BE.EP.PD

Abstract

It is well established that endothelial cells modulate vascular reactivity through the release of mediators such as prostacyclin, nitric oxide and endothelin. Catecholamines modulate vascular tone through actions on ±- and ²-adrenergic agents, however, the production and release of catecholamines are associated with the existence of nerve endings in vessels. Dopamine, a well-known neurotransmitter in the central nervous system, is also an important modulator of blood pressure, sodium balance and renal function, and adrenal function and is relevant to the pathogenesis and/or maintenance of hypertension. Interestingly, dopamine derivatives such as arachidonoyl-dopamine have been found in the central nervous system. It acts as an endogenous agonist at cannabinoid receptors. Another dopamine derivative, 6-nitro-dopamine, has also been identified as a basal release in human cord vessels (HUCV) in which it acts antagonizing D2-like receptors and also in rat vas deferens as a contractile agonist that is antagonized by tricyclic antidepressants . Nitrocatecholamines, such as nitronoradrenaline and nitroadrenaline, were extracted from the brain of rats and quantified by detecting a chemiluminescence reaction of LC-peroxoxalate and 6-nitronoradrenaline inhibited the transport of noradrenaline in rat synaptosomes. In this study, we will evaluate the release and physiological mechanism of nitro-catecholamines: 6-nitrodopamine, 6-nitronoradrenaline and 6-nitroadrenaline in the cardiovascular system.

Scientific publications

(14)

(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; FUGUHARA, VIVIAN; MONICA, FABIOLA Z. Z.; ANTUNES, EDSON; DE NUCCI, GILBERTO. Investigation on the positive chronotropic action of 6-nitrodopamine in the rat isolated atria. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. N/A, p. 12-pg., 2023-01-31. (19/16805-4, 17/15175-1, 21/13593-6, 21/14414-8, 22/07737-8)

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)

LIMA, ANTONIO TIAGO; BRITTO-JUNIOR, JOSE; MORAES, MANOEL ODORICO; MORAES, MARIA ELISABETE A.; FREGONESI, ADRIANO; MONICA, FABIOLA Z.; ANTUNES, EDSON; DE NUCCI, GILBERTO. 6-Nitrodopamine is an endogenous mediator of the rabbit corpus cavernosum relaxation. ANDROLOGY, v. 12, n. 6, p. 10-pg., 2023-12-29. (21/14414-8, 17/15175-1, 19/16805-4, 21/13593-6)

BRITTO, JOSE; DO PRADO, GUSTAVO L. PEREIRA; CHIAVEGATTO, SILVANA; CUNHA, FERNANDO; MORAES, MANOEL ODORICO; MORAES, MARIA ELISABETE A.; MONICA, FABIOLA Z.; ANTUNES, EDSON; DE NUCCI, GILBERTO. The importance of the endothelial nitric oxide synthase on the release of 6-nitrodopamine from mouse isolated atria and ventricles and their role on chronotropism. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 138, p. 8-pg., 2023-06-12. (17/15175-1, 19/16805-4, 21/14414-8)

LIMA, ANTONIO TIAGO; JABBOUR, SAMI; BRITTO-JUNIOR, JOSE; DE CARVALHO, DEMETRIO MARTINHO RAMOS; FREGONESI, ADRIANO; MARIANO, FERNANDA V.; DE SOUZA, VALERIA BARBOSA; SCHENKA, ANDRE ALMEIDA; ANTUNES, EDSON; DE NUCCI, GILBERTO. 6-Nitrodopamine potentiates catecholamine-induced contractions of human isolated vas deferens. FASEB BIOADVANCES, v. 7, n. 2, p. 9-pg., 2025-01-15. (19/16805-4, 17/15175-1, 21/13593-6, 21/14414-8, 21/13726-6)

OLIVEIRA, DENIS LIMA; CARDOSO, VINICIUS FRANCISCO; BRITTO-JUNIOR, JOSE; FUGUHARA, VIVIAN; FRECENTESE, FRANCESCO; SPARACO, ROSA; SANTAGADA, VINCENZO; CALIENDO, GIUSEPPE; PUPO, ANDRE SAMPAIO; ANTUNES, EDSON; et al. The negative chronotropic effects of (±)-propranolol and (±)-4-NO₂-propranolol in the rat isolated right atrium are due to blockade of the 6-nitrodopamine receptor. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. N/A, p. 12-pg., 2024-10-09. (21/14414-8, 22/07737-8, 17/15175-1, 19/16805-4)

J. BRITTO-JÚNIOR; A.T. LIMA; J.S. SANTOS-XAVIER; P. GONZALEZ; F.Z. MÓNICA; R. CAMPOS; V.B. DE SOUZA; A.A. SCHENKA; E. ANTUNES; G. DE NUCCI. Relaxation of thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) by endothelium-derived 6-nitrodopamine. Brazilian Journal of Medical and Biological Research, v. 56, 2023-04-07. (21/14414-8, 21/13593-6, 21/13726-6, 17/15175-1, 19/16805-4)

BRITTO-JUNIOR, JOSE; LIMA, ANTONIO TIAGO; CAMPOS, RAFAEL; GIAO, ALEXANDRE ASTURIANO; MENDES, GUSTAVO DUARTE; SILVA, LUIZA P. FERREIRA-NOVAES P.; FREGONESI, ADRIANO; PUPO, ANDRE SAMPAIO; ANTUNES, EDSON; DE NUCCI, GILBERTO. 6-Nitrodopamine potentiates contractions of rat isolated vas deferens induced by noradrenaline, adrenaline, dopamine and electric field stimulation. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. N/A, p. 16-pg., 2023-04-04. (21/14414-8, 17/15175-1, 19/16805-4, 22/08232-7, 22/06644-6, 21/13593-6)

DAL POZZO, CAROLINE FERNANDA SANCHES; MALDONADO JUNIOR, JOSE EDUARDO; BRITTO-JUNIOR, JOSE; BADIN, JOAO FELIPE AGOSTINI; DE SOUZA, VALERIA BARBOSA; SCHENKA, ANDRE ALMEIDA; PETERSON, LARRYN W.; FREGONESI, ADRIANO; ANTUNES, EDSON; DE NUCCI, GILBERTO. Basal release of 6-cyanodopamine from rat isolated vas deferens and its role on the tissue contractility. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 476, n. 8, p. 15-pg., 2024-07-04. (21/13726-6, 17/15175-1, 19/16805-4, 22/13062-3, 21/14414-8)

DE OLIVEIRA, MARIANA GONCALVES; BRITTO-JUNIOR, JOSE; DIAS, DOUGLAS RAFAEL MARTINS; PEREIRA, LUISE GABRIELA SANTOS; CHIAVEGATTO, SILVANA; HERMAWAN, IDAM; SHIMOKAWA, HIROAKI; TSUTSUI, MASATO; ANTUNES, EDSON; DE NUCCI, GILBERTO. Neurogenic-derived 6-nitrodopamine is the most potent endogenous modulator of the mouse urinary bladder relaxation. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 153, p. 8-pg., 2024-10-29. (17/06100-8, 21/14414-8, 23/09792-9, 19/16805-4)

DE OLIVEIRA, LUIS FREDERICO GERBASE; BRITTO JUNIOR, JOSE; LIMA, ANTONIO TIAGO; MORAES, MANOEL ODORICO; MORAES, MARIA ELISABETE A.; DE SOUZA, VALERIA BARBOSA; SCHENKA, ANDRE ALMEIDA; MONICA, FABIOLA ZAKIA; DE NUCCI, GILBERTO. Release of 6-nitrodopamine from human popliteal artery and vein. Life Sciences, v. 326, p. 9-pg., 2023-05-31. (21/14414-8, 17/15175-1, 19/16805-4, 21/13593-6, 21/13726-6)

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)

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)

CAMPOS, RAFAEL; NIEDERAUER, ANA JULIA SCHMIDT; BRITTO-JUNIOR, JOSE; DE SOUZA, VALERIA B.; SCHENKA, ANDRE A.; MONICA, FABIOLA Z.; MORAES, MANOEL ODORICO; MORAES, MARIA ELISABETE A.; ANTUNES, EDSON; DE NUCCI, GILBERTO. Basal release and relaxation responses to 6-nitrodopamine in swine carotid, coronary, femoral, and renal arteries. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, v. 285, p. 13-pg., 2024-08-17. (21/13726-6, 22/08232-7, 17/15175-1, 19/16805-4, 21/14414-8, 23/15350-9, 23/14557-9)