PARTICIPATION OF NO/GC/cGMP/K+ CHANNELS IN THE RELATATION INDUCED BY Crotalus durissus cascavella IN MESENTERIC ARTERY

Abstract

IntroductionThe studies with toxins from snakes poison have shown promising biological effects, especially those regarding to cardiovascular system, such as hypotensive and vasodilators.AimsTo investigate the vascular effect of Crotalus durissus cascavella poison (CDC), a high prevalence species in the state of Bahia ‐ Brazil, was used rat superior mesenteric artery.MethodsWistar rats (12–16 weeks/250–300g) were euthanized in CO2 camera and the mesenteric artery were isolated and free from connective tissue and cut into rings that was kept in Tyrode solution at 37°C carbonated with 95% of O2 and 5% of CO2. The amperometry technic was used to evaluate NO production in isolated aortic endothelial cells. The significant values was p<0.05.ResultsCumulative administration of the CDC (0.001 – 30μg/mL) relaxed phenylephrine‐induced contractions in a concentration‐dependent manner (Emax = 47.9 ± 5.0%; n=8) in the endothelial vascular presence, this effect was practically abolished in the endothelial vascular absence (Emax= 5.8 ± 2.4%; n=5; *** p<0.001). The vasorelaxant effect induced by CDC in KCl 80mM‐induced contraction was abolished (Emax= 6.4 ± 0.9%; n=5; *** p<0.001. Pre‐treatment with Indomethacin (10μM), L‐NAME (100μM), and ODQ (10μM) significantly attenuated the relaxation effect induced by CDC (Emax = 29.1 ± 7.1%, n = 6, Emax = 17.5 ± 2.2%, n = 6, Emax = 11.2 ± 3.5%, n = 6, respectively). Additionally, in studies with isolated aortic endothelial cells demonstrated that CDC in concentration of 10 and 90 μg/mL induced significant increase in NO production. In mesenteric rings pre incubated with KCl 20mM, to evaluate K+ channels participation, the vasorelaxant effect induced by CDC was significantly reduced (Emax = 21.3 ± 8%, n = 7). Similar results was observed in the presence of Iberiotoxin (100nM), BaCl2 (30μM) and 4‐aminopiridin (1mM) [(Emax = 13.0 ± 3 %, n= 5, Emax = 21.7 ± 8 %, n= 5 e Emax = 9.5 ± 1.3, %, n=5, respectively).ConclusionThose results suggest that the CDC induces vasorelaxant effects in isolated superior mesenteric artery rings from normotensive rats in an endothelium‐dependent way, possibly trough endothelium‐derived relaxing factors, especially the NO, resulting in guanylyl cyclase activation, followed by GMPc production and probably K+ channels activation (BKca, Kv and Kir). Additionally, prostanoids derivated from cyclooxygenase also are involved in the relaxant effect induced by CDC.3012 ‐ ASPET Cardiovascular Pharmacology – General/OtherSupport or Funding InformationFundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)