Adjuvant-induced arthritis promotes vascular hyporesponsiveness to phenylephrine through a nitric oxide-related mechanism

Autor(es)

T.S. Araujo ^[1] ; M.A. Spadella ^[2] ; C.P. Carlos ; C.R. Tirapelli ^[4] ; E.F.B. Chagas ; J.C.D. Pinheiro ^[6] ; A.B. Chies ^[7]

Afiliação do(s) autor(es)

^[1] Faculdade de Medicina de Marília. Laboratório de Farmacologia - Brasil

^[2] Faculdade de Medicina de Marília. Laboratório de Embriologia Humana - Brasil

^[4] Universidade de São Paulo. Escola de Enfermagem de Ribeirão Preto. Laboratório de Farmacologia Cardiovascular - Brasil

^[6] Faculdade de Medicina de Marília. Laboratório de Farmacologia - Brasil

^[7] Faculdade de Medicina de Marília. Laboratório de Farmacologia - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 57, 2024-05-17.

Resumo

Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway. (AU)

• Processo FAPESP: 16/08450-3 - Influência da testosterona nas alterações vasculares promovidas pela artrite induzida por adjuvante que envolvem a angiotensina II
• Beneficiário: Agnaldo Bruno Chies
• Modalidade de apoio: Auxílio à Pesquisa - Regular