D. Russelii venom mediates vasodilatation of resistance like arteries via activation of k v and k ca channels

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Abstract

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 μg/kg, i.v.) caused a 45 ± 8% decrease in blood pressure within 10 min of administration in anaesthetised (100 μg/kg ketamine/xylazine 10:1 ratio, i.p.) rats. Venom (1 ng/mL-1 μg/mL) caused concentration-dependent relaxation (EC 50 = 145.4 ± 63.6 ng/mL, R max = 92 ± 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 µM), 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 µM) and Ca 2+ -activated (K Ca : tetraethylammonium (TEA, 1000 µM), SK Ca : apamin (0.1 µM), IK Ca : TRAM-34 (1 µM), BK Ca , iberiotoxin (0.1 µM)) K + channels markedly attenuated venom-induced relaxation. Responses were unchanged in the presence of the ATP-sensitive K + channel blocker glibenclamide (10 µM), or H1 receptor antagonist, mepyramine (0.1 µM). 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 µM). In conclusion, D. russelii-venom-induced hypotension in rodents may be due to activation of K v and K Ca channels, leading to vasorelaxation predominantly via an endothelium-independent mechanism. Further investigation is required to identify the toxin(s) responsible for this effect.

Original languageEnglish
Article number197
Number of pages10
JournalToxins
Volume11
Issue number4
DOIs
Publication statusPublished - 1 Apr 2019

Keywords

  • D. russelii venom
  • Hypotension
  • Potassium channels
  • Vasodilatation

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