Relaxation of thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) by endothelium-derived 6-nitrodopamine

Author(s)

J. Britto-Júnior ^[1] ; A.T. Lima ^[2] ; J.S. Santos-Xavier ^[3] ; P. Gonzalez ^[4] ; F.Z. Mónica ^[5] ; R. Campos ; V.B. de Souza ^[7] ; A.A. Schenka ^[8] ; E. Antunes ^[9] ; G. De Nucci

Affiliation

^[1] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Farmacologia - Brasil

^[2] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Farmacologia - Brasil

^[3] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Farmacologia - Brasil

^[4] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Farmacologia - Brasil

^[5] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Farmacologia - Brasil

^[7] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Farmacologia - Brasil

^[8] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Farmacologia - Brasil

^[9] Universidade Estadual de Campinas. Faculdade de Ciências Médicas. Departamento de Farmacologia - Brasil

• Document type: Journal article
• Source: Brazilian Journal of Medical and Biological Research; v. 56, 2023-04-07.

Abstract

6-Nitrodopamine is a novel catecholamine released by vascular tissues, heart, and vas deferens. The aim of this study was to investigate whether 6-nitrodopamine is released from the thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) and to evaluate the relaxing and anti-contractile actions of this catecholamine. Release of 6-nitrodopamine, dopamine, noradrenaline, and adrenaline was assessed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The relaxations induced by 6-nitrodopamine and by the selective dopamine D2 receptor antagonist L-741,626 were evaluated on U-46619 (3 nM)-pre-contracted vessels. The effects of 6-nitrodopamine and L-741,626 on the contractions induced by electric-field stimulation (EFS), dopamine, noradrenaline, and adrenaline were also investigated. Both aorta and pulmonary artery rings exhibited endothelium-dependent release of 6-nitrodopamine, which was significantly reduced by the NO synthesis inhibitor L-NAME. Addition of 6-nitrodopamine or L-741,626 caused concentration-dependent relaxations of both vascular tissues, which were almost abolished by endothelium removal, whereas L-NAME and the soluble guanylate cyclase inhibitor ODQ had no effect on 6-nitrodopamine-induced relaxations. Additionally, pre-incubation with 6-nitrodopamine antagonized the dopamine-induced contractions, without affecting the noradrenaline- and adrenaline-induced contractions. Pre-incubation with L-741,626 antagonized the contractions induced by all catecholamines. The EFS-induced contractions were significantly increased by L-NAME, but unaffected by ODQ. Immunohistochemical assays showed no immunostaining of the neural tissue markers S-100 and calretinin in either vascular tissue. The results indicated that 6-nitrodopamine is the major catecholamine released by marmoset vascular tissues, and it acts as a potent and selective antagonist of dopamine D2-like receptors. 6-nitrodopamine release may be the major mechanism by which NO causes vasodilatation. (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: 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
• 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: 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