Author: Veras RC, Rodrigues KG, Alustau MD, Araújo IG, de Barros AL, Alves RJ, Nakao LS, Braga VA, Silva DF, de Medeiros IA.
Affiliation: *Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil; †Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Pampulha, Belo Horizonte, Minas Gerais, Brazil; ‡Departamento de Patologia Básica, Universidade Federal do Paraná, Jd. Americas, Curitiba, Paraná, Brazil; §Centro de Biotecnologia, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil; and ¶Departamento de Biorregulação, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
Conference/Journal: J Cardiovasc Pharmacol.
Date published: 2013 Jul 12
Other:
Volume ID: 62 , Issue ID: 1 , Pages: 58-66 , Word Count: 210
For many years, nitric oxide (NO) has been studied as an important mediator in the control of vascular tone. Endothelial deficiencies that diminish NO production can result in the development of several future cardiovascular diseases, such as hypertension and arteriosclerosis. In this context, new drugs with potential ability to donate NO have been studied. In this study, 3 aromatic oximes [benzophenone oxime, 4-Cl-benzophenone oxime, and E-cinnamaldehyde oxime (E-CAOx)] induced vasorelaxation in endothelium-denuded and intact superior mesenteric rings precontracted with phenylephrine. E-CAOx demonstrated the most potent effect, and its mechanism of action was evaluated. Vascular reactivity experiments demonstrated that the effect of E-CAOx was reduced by the presence of 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, 1H[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one, and (Rp)-8-(para-chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate, suggesting the participation of NO/sGC/PKG pathway. NO donation seems to be mediated through nicatinamide adenine dinucleotide phosphate-dependent reductases because 7-ethoxyresorufin decreased the effect of E-CAOx on vascular reactivity and reduced NO formation as detected by flow cytometry using the NO indicator diaminofluorescein 4,5-diacetate. Further downstream of NO donation, K subtype channels were also shown to be involved in the E-CAOx vasorelaxant effect. The present study showed that E-CAOx acts like an NO donor, activating NO/sGC/PKG pathway and thus K channels.
PMID: 23842292