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

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Author(s):
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
Total Authors: 10
Document type: Journal article
Source: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY; v. 262, p. 9-pg., 2022-12-01.
Abstract

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)

FAPESP's process: 21/13593-6 - Evaluation of chronic 6-nitrodopamine treatment in rats
Grantee:Antonio Tiago Silva Lima
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 21/13726-6 - Identification of molecules related to the synthesis of adrenaline, noradrenaline and dopamine in the endothelium of reptiles and mammals by immunohistochemistry and in situ hibridization
Grantee:Valéria Barbosa de Souza
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 19/16805-4 - Evaluation of the pathophysiological role of endothelial catecholamines
Grantee:Gilberto de Nucci
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 17/15175-1 - Modulation of soluble guanylate cyclase and the intracellular levels of cyclic nucleotides in the lower urinary tract and prostate
Grantee:Edson Antunes
Support Opportunities: Research Projects - Thematic Grants