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

Molecules

Bruna P. V. Dantas¹  Thaís P. Ribeiro¹  Valéria L. Assis¹  Fabíola F. Furtado¹  Kívia S. Assis¹  Jeziane S. Alves²  Tania M.S. Silva²  Celso A. Camara²  Maria S. Fran๺-Silva¹  Robson C. Veras¹  Isac A. Medeiros¹  Jacicarlos L. Alencar¹ 

[1] Biotechnology Center, Federal University of Paraíba, João Pessoa, PB 58.051-900, Brazil; E-Mails:;Molecular Sciences Department, Federal Rural University of Pernambuco, Recife, PE 52171-900, Brazil; E-Mails:

关键词: blood pressure;    mesenteric rings;    nitric oxide;    potassium channels;    vasodilation;    naphthoquinone oxime;   

DOI  :  10.3390/molecules19079773

来源: mdpi

【 摘 要 】

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 (OximeS1) 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 K_ir, K_v and K_ATP channels. We observed the involvement of BK_Ca 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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.