Endothelium-derived 6-nitrodopamine is the major mechanism by which nitric oxide relaxes the rabbit isolated aorta.

Autor: Santos EXD; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Britto-Júnior J; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Ribeiro JV; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.; Department of Pharmacology, Faculty São Leopoldo Mandic, Campinas, São Paulo, Brazil., Junior GQ; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Lima AT; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Moraes MO; Clinical Pharmacology Unit, Drug Research and Development Center, Federal University of Ceará (UFC), Fortaleza, Brazil., Moraes MEA; Clinical Pharmacology Unit, Drug Research and Development Center, Federal University of Ceará (UFC), Fortaleza, Brazil., Antunes E; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Schenka A; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., De Nucci G; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.; Department of Pharmacology, Faculty São Leopoldo Mandic, Campinas, São Paulo, Brazil.; Clinical Pharmacology Unit, Drug Research and Development Center, Federal University of Ceará (UFC), Fortaleza, Brazil.; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Frontiers in pharmacology [Front Pharmacol] 2024 Nov 21; Vol. 15, pp. 1507802. Date of Electronic Publication: 2024 Nov 21 (Print Publication: 2024).
DOI: 10.3389/fphar.2024.1507802
Abstrakt: 6-Nitrodopamine (6-ND) is the predominant catecholamine released from isolated vascular tissues in both mammals and reptiles, with its release being significantly reduced by the NO synthesis inhibitor, N ω -nitro-L-arginine methyl ester (L-NAME). The vasorelaxation induced by 6-ND is unaffected by either L-NAME or the soluble guanylate cyclase (sGC) inhibitor, ODQ, indicating an alternative mechanism of action. The vasorelaxant effect appears to be mediated through selective antagonism of dopamine D 2 receptors rather than traditional nitric oxide (NO)-mediated pathways. This study examined the basal release of 6-ND, dopamine, noradrenaline, and adrenaline from the rabbit thoracic aorta by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Additionally, the effects of 6-ND and the dopamine receptor antagonist L741,626 on relaxation responses and electric-field stimulation (EFS)-induced contractions in aortic rings were assessed. Nitric oxide pathway inhibitors, including L-NAME, ODQ, and methylene blue, were utilized to assess the involvement of this pathway in 6-ND-induced vasorelaxation. Concentration-response curves for norepinephrine, epinephrine, and dopamine were generated in the presence and absence of 6-ND and L-741,626. The rabbit isolated aorta presented the basal release of endothelium-derived dopamine and 6-ND. Furthermore, 6-nitrodopamine and L-741,626 induced concentration-dependent relaxations in endothelin-1 pre-contracted aortic rings. The relaxations were reduced by the mechanical removal of the endothelium but unaffected by pre-treatment with L-NAME, ODQ, or methylene blue. Pre-incubation with 6-ND significantly reduced dopamine-induced contractions, while noradrenaline- and adrenaline-induced contractions remained unchanged. The findings demonstrated that endothelium-derived 6-ND is the most potent endogenous relaxant of the rabbit isolated aorta, and the mechanism is independent of the NO pathway and involved the blockade of dopamine D2 receptors.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The reviewer AJ declared a shared affiliation with the author(s) GD to the handling editor at the time of review.
(Copyright © 2024 Santos, Britto-Júnior, Ribeiro, Junior, Lima, Moraes, Moraes, Antunes, Schenka and De Nucci.)
Databáze: MEDLINE
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