Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway
| Autor: | Jacicarlos Lima de Alencar, Celso A. Camara, Fabíola Fialho Furtado, Isac Almeida de Medeiros, Robson Cavalcante Veras, Tania M. S. Silva, Valdir A. Braga, Valéria L. Assis, Bruna Priscilla Vasconcelos Dantas, Thaís P. Ribeiro, Jeziane S. Alves, Maria S. França-Silva, Kívia S. Assis |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Vasodilator Agents Pharmaceutical Science Receptors Cytoplasmic and Nuclear Vasodilation Pharmacology Article Analytical Chemistry Nitric oxide lcsh:QD241-441 chemistry.chemical_compound Soluble Guanylyl Cyclase lcsh:Organic chemistry nitric oxide medicine.artery mesenteric rings Drug Discovery Oximes medicine Animals Nitric Oxide Donors Superior mesenteric artery Physical and Theoretical Chemistry vasodilation Cyclic GMP Aorta Lapachol Dose-Response Relationship Drug Organic Chemistry blood pressure naphthoquinone oxime Oxime Hydroxocobalamin potassium channels Naphthoquinone Rats chemistry Biochemistry Chemistry (miscellaneous) Guanylate Cyclase Molecular Medicine medicine.drug Naphthoquinones Signal Transduction |
| Zdroj: | Molecules, Vol 19, Iss 7, Pp 9773-9785 (2014) Molecules Volume 19 Issue 7 Pages 9773-9785 |
| ISSN: | 1420-3049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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