title: Participation of nitric oxide pathway in the relaxation response induced by E-cinnamaldehyde oxime in superior mesenteric artery isolated from rats.
abstract: 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.
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.
authors.forename: Robson C
authors.initials: RC
authors.lastname: Veras
authors.forename: Karoline G
authors.initials: KG
authors.lastname: Rodrigues
authors.forename: Maria do C
authors.initials: Mdo C
authors.lastname: Alustau
authors.forename: Islânia G A
authors.initials: IG
authors.lastname: Araújo
authors.forename: André Luis B
authors.initials: AL
authors.lastname: de Barros
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Alves
authors.forename: Lia S
authors.initials: LS
authors.lastname: Nakao
authors.forename: Valdir A
authors.initials: VA
authors.lastname: Braga
authors.forename: Darizy F
authors.initials: DF
authors.lastname: Silva
authors.forename: Isac A
authors.initials: IA
authors.lastname: de Medeiros
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D049449:Luminescence; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D020030:Nitric Oxide Donors; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D010091:Oximes / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010091:Oximes; D015221:Potassium Channels; D009569:Nitric Oxide; D000171:Acrolein; D052250:Nitric Oxide Synthase Type III; C012843:cinnamaldehyde; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester