Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway
AbstractIt has been established that oximes cause endothelium-independent relaxation in blood vessels. In the present study, the cardiovascular effects of the new oxime 3-hydroxy-4–(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one (Oxime S1) derived from lapachol were evaluated. In normotensive rats, administration of Oxime S1 (10, 15, 20 and 30 mg/Kg, i.v.) produced dose-dependent reduction in blood pressure. In isolated aorta and superior mesenteric artery rings, Oxime S1 induced endothelium-independent and concentration-dependent relaxations (10−8 M to 10−4 M). In addition, Oxime S1-induced vasorelaxations were attenuated by hydroxocobalamin or methylene blue in aorta and by PTIO or ODQ in mesenteric artery rings, suggesting a role for the nitric oxide (NO) pathway. Additionally, Oxime S1 (30 and 100 µM) significantly increased NO concentrations (13.9 ± 1.6 nM and 17.9 ± 4.1 nM, respectively) measured by nitric oxide microsensors. Furthermore, pre-contraction with KCl (80 mM) prevented Oxime S1-derived vasorelaxation in endothelium-denuded aortic rings. Of note, combined treatment with potassium channel inhibitors also reduced Oxime S1-mediated vasorelaxation suggesting a role for potassium channels, more precisely Kir, Kv and KATP channels. We observed the involvement of BKCa channels in Oxime S1-induced relaxation in mesenteric artery rings. In conclusion, these data suggest that the Oxime S1 induces hypotension and vasorelaxation via NO pathway by activating soluble guanylate cyclase (sGC) and K+ channels. View Full-Text
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Dantas, B.P.V.; Ribeiro, T.P.; Assis, V.L.; Furtado, F.F.; Assis, K.S.; Alves, J.S.; Silva, T.M.; Camara, C.A.; França-Silva, M.S.; Veras, R.C.; Medeiros, I.A.; Alencar, J.L.; Braga, V.A. Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway. Molecules 2014, 19, 9773-9785.
Dantas BPV, Ribeiro TP, Assis VL, Furtado FF, Assis KS, Alves JS, Silva TM, Camara CA, França-Silva MS, Veras RC, Medeiros IA, Alencar JL, Braga VA. Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway. Molecules. 2014; 19(7):9773-9785.Chicago/Turabian Style
Dantas, Bruna P.V.; Ribeiro, Thaís P.; Assis, Valéria L.; Furtado, Fabíola F.; Assis, Kívia S.; Alves, Jeziane S.; Silva, Tania M.; Camara, Celso A.; França-Silva, Maria S.; Veras, Robson C.; Medeiros, Isac A.; Alencar, Jacicarlos L.; Braga, Valdir A. 2014. "Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway." Molecules 19, no. 7: 9773-9785.