{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:58:35Z","timestamp":1767905915901,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":3999,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1998,3]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The effects of the K<jats:sup>+<\/jats:sup> channel opener levcromakalim, the guanylate cyclase stimulant nitroprusside and the dual drug nicorandil (K<jats:sup>+<\/jats:sup> channel opener and guanylate cyclase stimulant) were analysed in piglet isolated endothelium\u2010denuded pulmonary (PA) and mesenteric (MA) arteries stimulated by noradrenaline (NA) or by the thromboxane A<jats:sub>2<\/jats:sub> mimetic U46619.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Nicorandil, levcromakalim and verapamil were less potent in PA than in MA, the efficacy of levcromakalim was also reduced in PA. The effects of nicorandil and levcromakalim were similar in arteries pre\u2010contracted by NA and U46619, whereas verapamil was more potent in arteries pre\u2010contracted by NA. Nitroprusside was equipotent in MA pre\u2010contracted by either NA or U46619 and in PA pre\u2010contracted by NA whereas in PA pre\u2010contracted by U46619, nitroprusside showed lower potency and efficacy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The relaxant effects of levcromakalim and nitroprusside were inhibited by 10<jats:sup>\u22125<\/jats:sup>\u2003<jats:sc>M<\/jats:sc> glibenclamide and 10<jats:sup>\u22126<\/jats:sup>\u2003<jats:sc>M<\/jats:sc> ODQ, respectively. Nicorandil\u2010induced relaxation was inhibited by ODQ in all experimental conditions, whereas glibenclamide had inhibitory effects in PA and MA pre\u2010contracted by U46619, had no effect in PA pre\u2010contracted by NA and in MA pre\u2010contracted by NA it was only inhibitory in the presence of ODQ.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>No apparent interactions were found between nitroprusside and levcromakalim as indicated by the lack of effects of pretreatment with one of them (producing 20\u201335% relaxation) on the potency of the relaxant response to the other. However, in PA pre\u2010contracted by U46619, where nitroprusside or levcromakalim induced only partial relaxation, the combination of both mechanisms (either by combining nitroprusside plus levcromakalim or by nicorandil) was able to induce full vasodilatation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, K<jats:sup>+<\/jats:sup> channel opening and guanylate cyclase stimulation are independent pathways that induce additive vasorelaxation in piglet PA and MA. The mechanism of action of nicorandil is dependent on the artery and on the nature of the agonist employed to precontract the artery. The relative efficacy of K<jats:sup>+<\/jats:sup> channel opening vs guanylate cyclase stimulation may partially explain the preferential contribution of each mechanism to the relaxant effects of nicorandil.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>123<\/jats:bold>, 847\u2013854; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701693\">10.1038\/sj.bjp.0701693<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701693","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:24:26Z","timestamp":1106940266000},"page":"847-854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Role of K<sup>+<\/sup> channel opening and stimulation of cyclic GMP in the vasorelaxant effects of nicorandil in isolated piglet pulmonary and mesenteric arteries: relative efficacy and interactions between both pathways"],"prefix":"10.1111","volume":"123","author":[{"given":"Francisco","family":"P\u00e9rez\u2010Vizca\u00edno","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angel L.","family":"Cogolludo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Villamor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Tamargo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199510000-00006"},{"key":"e_1_2_6_3_1","first-page":"526","article-title":"Nicorandil: differential contribution of K+ channel opening and guanylate cyclase stimulation to its vasorelaxant effects on various endothelin\u20101\u2010contracted arterial preparations. 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