{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T15:48:38Z","timestamp":1761580118076},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":2162,"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":[[2003,3]]},"abstract":"<jats:p>It is widely established that in rat mesenteric arteries, endothelium\u2010derived hyperpolarizing factor (EDHF)\u2010mediated relaxation evoked by acetylcholine is abolished by a combination of charybdotoxin plus apamin. 4\u2010Aminopyridine, an inhibitor of voltage\u2010gated (Kv) K<jats:sup>+<\/jats:sup>\u2010channels, in combination with apamin had moderate effects on the EDHF\u2010mediated relaxation. Maurotoxin (MTX), an inhibitor of Kv and intermediate\u2010conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup>\u2010channels (IK), had no effect on EDHF\u2010mediated relaxation. However, MTX in combination with apamin completely abolished EDHF\u2010mediated relaxation and endothelial cell hyperpolarization. The selective IK inhibitor 2\u2010(2\u2010chlorophenyl)\u20102,2\u2010diphenyl acetonitrile (TRAM\u201039) had no significant effect on EDHF\u2010mediated relaxation. EDHF\u2010mediated vasorelaxation and hyperpolarization was abolished by a combination of TRAM\u201039 and apamin. These data demonstrate two new combinations of K<jats:sup>+<\/jats:sup>\u2010channel inhibitors for the investigation of EDHF. Furthermore, by using TRAM\u201039, a potent selective inhibitor of IK channels, we provide the first <jats:italic>direct<\/jats:italic> evidence that abolition of EDHF requires the simultaneous presence of intermediate\u2010 and small\u2010conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup>\u2010channel inhibitors.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>138<\/jats:bold>, 1031\u20131035. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705171\">10.1038\/sj.bjp.0705171<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705171","type":"journal-article","created":{"date-parts":[[2003,4,8]],"date-time":"2003-04-08T17:04:06Z","timestamp":1049821446000},"page":"1031-1035","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Inhibition of EDHF by two new combinations of K<sup>+<\/sup>\u2010channel inhibitors in rat isolated mesenteric arteries"],"prefix":"10.1111","volume":"138","author":[{"given":"Jane M","family":"Hinton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip D","family":"Langton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.2.409"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.276.3.H1107"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701778"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702916"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/46816"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.1.C1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704348"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(01)00028-4"},{"key":"e_1_2_8_10_1","article-title":"Possible involvement of voltage\u2010dependent potassium channels in the EDHF\u2010mediated relaxation of rat mesenteric artery","author":"HINTON J.M.","year":"2001","journal-title":"J. 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