D. russelii venom mediates vasodilatation of resistance like arteries via activation of Kv and KCa Channels

摘要: Russell's viper (Daboia russelii) venom causes a range of clinical effects in humans. Hypotension is an uncommon but severe complication envenoming. The mechanism(s) responsible for this effect are unclear. In study, we examined the cardiovascular Sri Lankan D. russelii anaesthetised rats and isolated mesenteric arteries. (100 μg/kg, i.v.) caused 45 ± 8% decrease blood pressure within 10 min administration μg/kg ketamine/xylazine 10:1 ratio, i.p.) rats. Venom (1 ng/mL⁻1 μg/mL) concentration-dependent relaxation (EC50 = 145.4 63.6 ng/mL, Rmax 92 2%) U46619 pre-contracted rat small arteries mounted myograph. Vasorelaxant potency was unchanged presence nitric oxide synthase inhibitor, L-NAME µM), or removal endothelium. high K⁺ (30 mM), vasorelaxant response to abolished. Similarly, blocking voltage-dependent (Kv: 4-aminopryidine; 1000 µM) Ca2+-activated (KCa: tetraethylammonium (TEA; µM); SKCa: apamin (0.1 IKCa: TRAM-34 BKCa; iberiotoxin µM)) channels markedly attenuated venom-induced relaxation. Responses were ATP-sensitive channel blocker glibenclamide (10 H1 receptor antagonist, mepyramine µM). Venom-induced vasorelaxtion also decreased transient potential cation subfamily V member 4 (TRPV4) RN-1734 conclusion, russelii-venom-induced hypotension rodents may be due activation Kv KCa channels, leading vasorelaxation predominantly via endothelium-independent mechanism. Further investigation required identify toxin(s) effect.