{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:56:18Z","timestamp":1791575778460,"version":"4.3.4"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Human envenoming by Australian brown snakes (<jats:italic>Pseudonaja<\/jats:italic> spp.) may result in potentially life-threatening hypotension and subsequent cardiovascular collapse. There have been relatively few studies of the cardiovascular and sympathetic effects of <jats:italic>Pseudonaja<\/jats:italic> spp. venoms. In this study, we have examined the effects of venom from five brown snake species\u2014<jats:italic>P. affinis<\/jats:italic>, <jats:italic>aspidorhyncha, inframacula, nuchalis,<\/jats:italic> and <jats:italic>textilis<\/jats:italic>\u2014on cardiac inotropic and chronotropic responses, vascular tone, and sympathetic nerve-induced vascular contractions in rat isolated tissues. The role of phospholipases A<jats:sub>2<\/jats:sub> (PLA<jats:sub>2<\/jats:sub>s) in venom-induced effects was assessed with the sPLA<jats:sub>2<\/jats:sub> inhibitor varespladib. In rat isolated left and right atria, there were no physiologically relevant effects of <jats:italic>Pseudonaja<\/jats:italic> venoms (0.1\u201330\u00a0\u00b5g\/ml) on left atrial force of contraction (inotropy) or right atrial rate (chronotropy). In contrast, in isolated small mesenteric arteries precontracted with a thromboxane mimetic, each of the five brown snake venoms (at 30\u00a0\u00b5g\/ml) caused marked vasorelaxation (\u221260 to \u201390% of contractile tone). Pretreatment with varespladib (1\u00a0\u00b5M) significantly inhibited the vasorelaxation caused by <jats:italic>P. aspidorhyncha<\/jats:italic>, <jats:italic>P. nuchalis,<\/jats:italic> and <jats:italic>P. textilis<\/jats:italic> venoms. Electrically induced sympathetic nerve-mediated contractions of mesenteric arteries were significantly attenuated by only <jats:italic>P. textilis<\/jats:italic>, and <jats:italic>P. affinis<\/jats:italic> venoms (30\u00a0\u00b5g\/ml) and these sympatholytic effects were inhibited by varespladib (1\u00a0\u00b5M). Based on their inhibition with the sPLA<jats:sub>2<\/jats:sub> inhibitor varespladib, we conclude that PLA<jats:sub>2<\/jats:sub> toxins in <jats:italic>P. aspidorhyncha<\/jats:italic>, <jats:italic>P. nuchalis<\/jats:italic>, and <jats:italic>P. textilis<\/jats:italic> venoms are involved in brown snake venom-induced vasorelaxation and the sympatholytic effects of <jats:italic>P. affinis<\/jats:italic>, and <jats:italic>P. textilis<\/jats:italic> venoms. Our study supports the promising potential role of varespladib as an initial (pre-referral) and\/or adjunct (in combination with antivenom) therapeutic agent for brown snake envenoming.<\/jats:p>","DOI":"10.3389\/fphar.2021.754304","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T06:44:30Z","timestamp":1634798670000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Role of Phospholipases A2 in Vascular Relaxation and Sympatholytic Effects of Five Australian Brown Snake, Pseudonaja spp., Venoms in Rat Isolated Tissues"],"prefix":"10.3389","volume":"12","author":[{"given":"Nhi Thuc","family":"Vuong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy N. 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