%0 Journal Article %T D. russelii Venom Mediates Vasodilatation of Resistance Like Arteries via Activation of Kv and KCa Channels %A Barbara K. Kemp-Harper %A Geoffrey K. Isbister %A Lachlan D. Rash %A Rahini Kakumanu %A Sanjaya Kuruppu %A Wayne C. Hodgson %J Archive of "Toxins". %D 2019 %R 10.3390/toxins11040197 %X Russell¡¯s viper (Daboia russelii) venom causes a range of clinical effects in humans. Hypotension is an uncommon but severe complication of Russell¡¯s viper envenoming. The mechanism(s) responsible for this effect are unclear. In this study, we examined the cardiovascular effects of Sri Lankan D. russelii venom in anaesthetised rats and in isolated mesenteric arteries. D. russelii venom (100 ¦Ìg/kg, i.v.) caused a 45 ¡À 8% decrease in blood pressure within 10 min of administration in anaesthetised (100 ¦Ìg/kg ketamine/xylazine 10:1 ratio, i.p.) rats. Venom (1 ng/mL¨C1 ¦Ìg/mL) caused concentration-dependent relaxation (EC50 = 145.4 ¡À 63.6 ng/mL, Rmax = 92 ¡À 2%) in U46619 pre-contracted rat small mesenteric arteries mounted in a myograph. Vasorelaxant potency of venom was unchanged in the presence of the nitric oxide synthase inhibitor, L-NAME (100 ¦ÌM), or removal of the endothelium. In the presence of high K+ (30 mM), the vasorelaxant response to venom was abolished. Similarly, blocking voltage-dependent (Kv: 4-aminopryidine; 1000 ¦ÌM) and Ca2+-activated (KCa: tetraethylammonium (TEA; 1000 ¦ÌM); SKCa: apamin (0.1 ¦ÌM); IKCa: TRAM-34 (1 ¦ÌM); BKCa; iberiotoxin (0.1 ¦ÌM)) K+ channels markedly attenuated venom-induced relaxation. Responses were unchanged in the presence of the ATP-sensitive K+ channel blocker glibenclamide (10 ¦ÌM), or H1 receptor antagonist, mepyramine (0.1 ¦ÌM). Venom-induced vasorelaxtion was also markedly decreased in the presence of the transient receptor potential cation channel subfamily V member 4 (TRPV4) antagonist, RN-1734 (10 ¦ÌM). In conclusion, D. russelii-venom-induced hypotension in rodents may be due to activation of Kv and KCa channels, leading to vasorelaxation predominantly via an endothelium-independent mechanism. Further investigation is required to identify the toxin(s) responsible for this effect %K D. russelii venom %K hypotension %K potassium channels %K vasodilatation %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520720/