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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1507802

ENDOTHELIUM-DERIVED 6-NITRODOPAMINE IS THE MAJOR MECHANISM BY WHICH NITRIC OXIDE RELAXES RABBIT ISOLATED AORTA

Provisionally accepted
Eric X. Santos Eric X. Santos 1José Britto-Júnior José Britto-Júnior 1*João V. Gomes João V. Gomes 1,2Gilberto Q. Junior Gilberto Q. Junior 1Antonio T. Lima Antonio T. Lima 1Manoel O. Moraes Manoel O. Moraes 3Maria E. Moraes Maria E. Moraes 3EDSON ANTUNES EDSON ANTUNES 1André Schenka André Schenka 1Gilberto De Nucci Gilberto De Nucci 1,2,4
  • 1 State University of Campinas, Campinas, Brazil
  • 2 São Leopoldo Mandic School, Campinas, São Paulo, Brazil
  • 3 Federal University of Ceara, Fortaleza, Ceará, Brazil
  • 4 University of São Paulo, São Paulo, Rio Grande do Sul, Brazil

The final, formatted version of the article will be published soon.

    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, 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 D2 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 LC-MS/MS. Additionally, the effects of 6-ND and the dopamine receptor antagonist L-741,626 on relaxation responses and electric field stimulation (EFS) in aortic rings were assessed. Nitric oxide pathway inhibitors, including L-NAME, ODQ, and methylene blue, were utilized to involvement of this pathway in the 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. Rabbit isolated aorta presented basal release of endothelium-derived dopamine and 6-ND. 6-Nitrodopamine and L-741,626 induced concentration-dependent relaxations in endothelin-1 pre-contracted aortic rings. The relaxations were reduced by 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 rabbit isolated aorta, the mechanism is independent of NO pathway and involved blockade of dopamine D2 receptors.

    Keywords: Indomethacin, cyclo-oxygenase, Cyclic GMP, Acetylcholine, endothelium-dependent hyperpolarization factor

    Received: 08 Oct 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Santos, Britto-Júnior, Gomes, Junior, Lima, Moraes, Moraes, ANTUNES, Schenka and De Nucci. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: José Britto-Júnior, State University of Campinas, Campinas, Brazil

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.