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Molecules 2014, 19(7), 9773-9785; https://doi.org/10.3390/molecules19079773

Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway

1
Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil
2
Molecular Sciences Department, Federal Rural University of Pernambuco, Recife, PE 52171-900, Brazil
*
Author to whom correspondence should be addressed.
Received: 19 May 2014 / Revised: 21 June 2014 / Accepted: 23 June 2014 / Published: 8 July 2014
(This article belongs to the Section Medicinal Chemistry)
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Abstract

It 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
Keywords: blood pressure; mesenteric rings; nitric oxide; potassium channels; vasodilation; naphthoquinone oxime blood pressure; mesenteric rings; nitric oxide; potassium channels; vasodilation; naphthoquinone oxime
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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.

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