Evaluation of chronic 6-nitrodopamine treatment in rats

• Grant number: 21/13593-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2022
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Gilberto de Nucci
• Grantee: Antonio Tiago Silva Lima
• 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

Electric Field Stimulation (EFS) is a technique in which an electrical stimulus is uniformly applied to isolated tissue in short-wave pulses. Depending on the mediators released by the EFS, tissue contraction or relaxation may occur. Initially, our research group demonstrated that stimulated contractions of Human Umbilical Cord Vessels (HUCV) depend on the presence of the endothelium and are not affected by tetrodotoxin, a sodium channel blocker used to prevent the release of mediators from nerve endings. Similar findings were found in reptiles, aorta of the tortoise Chelonoidis carbonaria and aorta of Crotalus durissus terrificus, Bothrops jararaca and Panterophis guttatus. Recently, the basal release of dopamine by HUCV endothelial cells was detected through pharmacological assays and by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). Dopamine acts in dopaminergic neurotransmission in the central nervous system, in the modulation of blood pressure by renal and vascular mechanisms, and is important in the modulation of cardiac function. LC-MS-MS analyzes also revealed a new vascular mediator to 6-nitrodopamine. 6-nitrodopamine is produced from the nitration of dopamine. Preliminary trials by our research group identified that 6-nitrodopamine has an important positive chronotropic effect in the right atrium of rats and in modulating their blood pressure. The aim of this work is to characterize and investigate the physiological role of the novel catecholamine 6-nitrodopamine in chronically treated rats. (AU)

Scientific publications

(11)

(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)

LIMA, ANTONIO TIAGO; AMORIM, AMANDA CONSULIN; BRITTO-JUNIOR, JOSE; CAMPITELLI, RAQUEL RIOS; FREGONESI, ADRIANO; MONICA, FABIOLA Z.; ANTUNES, EDSON; DE NUCCI, GILBERTO. beta(1)- and beta(1)/beta(2)-adrenergic receptor antagonists block 6-nitrodopamine-induced contractions of the rat isolated epididymal vas deferens. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. 395, n. 10, p. 12-pg., 2022-07-08. (21/14120-4, 19/16805-4, 17/15175-1, 21/13593-6)

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)

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)

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)

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)

LIMA, ANTONIO TIAGO; DOS SANTOS, ERIC XAVIER; BRITTO-JUNIOR, JOSE; DE SOUZA, VALERIA B.; SCHENKA, ANDRE A.; CAMPOS, RAFAEL; MORAES, MANOEL ODORICO; MORAES, MARIA ELISABETE A.; ANTUNES, EDSON; DE NUCCI, GILBERTO. Release of 6-nitrodopamine modulates vascular reactivity of Pantherophis guttatus aortic rings. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, v. 262, p. 9-pg., 2022-12-01. (21/13593-6, 21/13726-6, 19/16805-4, 17/15175-1)

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; CAMPOS, RAFAEL; PEIXOTO, MATHEUS; LIMA, ANTONIO TIAGO; JACINTHO, FELIPE FERNANDES; MONICA, FABIOLA Z.; MORENO, RONILSON AGNALDO; ANTUNES, EDSON; DE NUCCI, GILBERTO. 6-Nitrodopamine is an endogenous selective dopamine receptor antagonist in Chelonoidis carbonaria aorta. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, v. 260, p. 7-pg., 2022-07-07. (19/16805-4, 17/15175-1, 18/24971-9, 21/13593-6)

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)

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)