{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:48:07Z","timestamp":1790826487551,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1110343"],"award-info":[{"award-number":["1110343"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1061041"],"award-info":[{"award-number":["1061041"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Russell\u2019s viper (Daboia russelii) venom causes a range of clinical effects in humans. Hypotension is an uncommon but severe complication of Russell\u2019s 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 \u03bcg\/kg, i.v.) caused a 45 \u00b1 8% decrease in blood pressure within 10 min of administration in anaesthetised (100 \u03bcg\/kg ketamine\/xylazine 10:1 ratio, i.p.) rats. Venom (1 ng\/mL\u20131 \u03bcg\/mL) caused concentration-dependent relaxation (EC50 = 145.4 \u00b1 63.6 ng\/mL, Rmax = 92 \u00b1 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 \u00b5M), 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 \u00b5M) and Ca2+-activated (KCa: tetraethylammonium (TEA; 1000 \u00b5M); SKCa: apamin (0.1 \u00b5M); IKCa: TRAM-34 (1 \u00b5M); BKCa; iberiotoxin (0.1 \u00b5M)) K+ channels markedly attenuated venom-induced relaxation. Responses were unchanged in the presence of the ATP-sensitive K+ channel blocker glibenclamide (10 \u00b5M), or H1 receptor antagonist, mepyramine (0.1 \u00b5M). 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 \u00b5M). 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.<\/jats:p>","DOI":"10.3390\/toxins11040197","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T03:21:26Z","timestamp":1554175286000},"page":"197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["D. russelii Venom Mediates Vasodilatation of Resistance Like Arteries via Activation of Kv and KCa Channels"],"prefix":"10.3390","volume":"11","author":[{"given":"Rahini","family":"Kakumanu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing &amp; Health Sciences, Monash University, Clayton VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjaya","family":"Kuruppu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3616-0279","authenticated-orcid":false,"given":"Lachlan D.","family":"Rash","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, St Lucia QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey K.","family":"Isbister","sequence":"additional","affiliation":[{"name":"Clinical Toxicology Research Group, University of Newcastle, Callaghan NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne C.","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing &amp; Health Sciences, Monash University, Clayton VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara K.","family":"Kemp-Harper","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing &amp; Health Sciences, Monash University, Clayton VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chippaux, J.P. 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