Release of 6-nitrodopamine from human popliteal artery and vein

Author(s)

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

• Document type: Journal article
• Source: Life Sciences; v. 326, p. 9-pg., 2023-05-31.

Abstract

6-Nitrodopamine (6-ND) is a novel catecholamine that is released from human umbilical cord vessels, and it causes vascular relaxation by acting as a dopamine D2-receptor antagonist. Here it was investigated whether human peripheral vessels obtained from patients who have undergone surgery for leg amputation release 6-ND, and its action in these tissues. Popliteal artery and vein strips present basal release of 6-ND, as measured by liquid chromatography coupled to tandem mass spectrometry. The release was significantly reduced when the tissues were pre-treated with the nitric oxide synthase inhibitor L-NAME (100 & mu;M), or when the endothelium was mechanically removed. In U-46619 (3 nM) pre-contracted rings, 6-ND induced concentration-dependent re-laxations (pEC50 8.18 & PLUSMN; 0.05 and 8.40 & PLUSMN; 0.08, in artery and vein rings, respectively). The concentration -dependent relaxations induced by 6-ND were unaffected in tissues pre-treated with L-NAME, but significantly reduced in tissues where the endothelium has been mechanically removed. In U-46619 (3 nM) pre-contracted rings, the selective dopamine D2 receptor antagonist L-741,626 also caused concentration-dependent re-laxations (pEC50 8.92 & PLUSMN; 0.22 and 8.79 & PLUSMN; 0.19, in artery and vein rings, respectively). The concentration -dependent relaxations induced by L-741,626 were unaffected in tissues pre-treated with L-NAME, but signifi-cantly reduced in tissues where the endothelium has been mechanically removed. This is the first demonstration that 6-nitrodopamine is released from human peripheral artery and vein rings. The results also indicate that endothelium-derived dopamine is a major contractile agent in the popliteal artery and vein, and that selective dopamine D2-receptor antagonists such as 6-ND, may have therapeutic potential in the treatment of human peripheral vascular diseases. (AU)

• FAPESP's process: 21/14414-8 - Evaluation of the action of nitro-catecholamines in the cardiovascular system
• Grantee: José Britto Júnior
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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
• 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: 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