Release of 6-nitrodopamine modulates vascular reactivity of Pantherophis guttatus aortic rings

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY; v. 262, p. 9-pg., 2022-12-01.

Resumo

6-Nitrodopamine (6-ND) is a novel catecholamine that is released from human umbilical cord vessels and Chelonoidis carbonaria aortic rings. The synthesis/release of 6-ND is inhibited by either pre-incubation of the vessels with the nitric oxide (NO) synthase inhibitor L-NAME or by mechanical removal of the endothelium. 6 -ND causes powerful vasorelaxation, acting as a potent and selective dopamine D2-like receptor antagonist.Basal release of 6-ND from Panterophis guttatus endothelium intact and denuded aortic rings was quantified by LC-MS/MS. In order to evaluate the interaction of 6-ND with other catecholamines, aortic rings were suspended vertically between two metal hooks in 10-mL organ baths containing Krebs-Henseleit's solution and attached to isometric transducers.Endothelium intact aortic rings presented basal release of 6-ND, which was significantly reduced by previous incubation with L-NAME (100 mu M). In endothelin-1 (3 nM) pre-contracted endothelium intact aortic rings, 6-ND (10pM-1 mu M) and the dopamine D2-receptor antagonist L-761,626 (10 pM-1 mu M) induced concentration -dependent relaxations, which were not affected by incubation with L-NAME but greatly reduced in endothelium-removed aortic rings.6-ND (0.1-1 mu M) produced significant rightward shifts of the concentration-response curves to dopamine in L -NAME pre-treated endothelium-intact (pA2 7.01) rings. Contractions induced by noradrenaline and adrenaline were not affected by pre-incubation with 6-ND (1 mu M). The EFS-induced contractions of L-NAME pre-treated endothelium-intact aortic rings were significantly inhibited by incubation with 6-ND (1 mu M).The results indicate that 6-ND released from Pantherophis guttatus aortic rings is coupled to NO release and represents a new mechanism by which NO can modulate vascular reactivity independently of cGMP production. (AU)

• Processo FAPESP: 21/13593-6 - Avaliação do tratamento crônico da 6-nitrodopamina em ratos
• Beneficiário: Antonio Tiago Silva Lima
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 21/13726-6 - Identificação de moléculas relacionadas à síntese de adrenalina, noradrenalina e dopamina no endotélio de répteis e mamíferos, por meio de técnicas imuno-histoquímicas e moleculares in situ
• Beneficiário: Valéria Barbosa de Souza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/16805-4 - Avaliação do papel fisiopatológico das catecolaminas endoteliais
• Beneficiário: Gilberto de Nucci
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata
• Beneficiário: Edson Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Temático