{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T12:53:28Z","timestamp":1762001608591,"version":"build-2065373602"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,1,16]],"date-time":"2018-01-16T00:00:00Z","timestamp":1516060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005378","name":"Hacettepe \u00dcniversitesi","doi-asserted-by":"publisher","award":["7655"],"award-info":[{"award-number":["7655"]}],"id":[{"id":"10.13039\/501100005378","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endothelial<jats:styled-content style=\"fixed-case\">IK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>and\/or<jats:styled-content style=\"fixed-case\">SK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>channels play an important role in the control of vascular tone by participating in endothelium\u2010dependent relaxation. Whether \u03b2\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>antagonists, mainly used in hypertension, affect endothelial<jats:styled-content style=\"fixed-case\">K<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>channel function is unknown. In this study, we examined the effect of the \u03b22\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>antagonist and inverse agonist<jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>118,551 on the<jats:styled-content style=\"fixed-case\">IK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>\/<jats:styled-content style=\"fixed-case\">SK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>channel activity by assessing functional relaxation responses to several agonists that stimulate these channels. Mesenteric arterial rings isolated from male Sprague Dawley mounted to organ baths. Acetylcholine elicited<jats:styled-content style=\"fixed-case\">IK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>\u2010 and<jats:styled-content style=\"fixed-case\">SK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>\u2010mediated relaxations that were abolished by<jats:styled-content style=\"fixed-case\">TRAM<\/jats:styled-content>\u201034 and apamin, respectively.<jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>118,551, which did not dilate the arteries<jats:italic>per se<\/jats:italic>, increased the<jats:styled-content style=\"fixed-case\">IK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>\u2010mediated relaxations, whereas<jats:styled-content style=\"fixed-case\">SK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>\u2010mediated relaxations remained unaltered. Same potentiating effect was also detected on the<jats:styled-content style=\"fixed-case\">IK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>\u2010mediated relaxations to carbachol and A23187, but not to<jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>309. Neither acetylcholine\u2010induced nitric oxide\u2010mediated relaxations nor<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>relaxations changed with ICI 118,551. The<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>inhibitor<jats:styled-content style=\"fixed-case\">KT<\/jats:styled-content>\u20105720, the selective \u03b22\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>agonist salbutamol, the selective \u03b22\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>antagonist butoxamine, the non\u2010selective \u03b2\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>antagonist propranolol, and the inverse agonists carvedilol or nadolol failed to affect the<jats:styled-content style=\"fixed-case\">IK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>\u2010mediated relaxations.<jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>118,551\u2010induced increase was not reversed by salbutamol or propranolol as well. Besides, low potassium\u2010induced relaxations in endothelium\u2010removed arteries remained the same in the presence of<jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>118,551. These data demonstrate a previously unrecognized action of<jats:styled-content style=\"fixed-case\">ICI<\/jats:styled-content>118,551, the ability to potentiate endothelial<jats:styled-content style=\"fixed-case\">IK<jats:sub>C<\/jats:sub><\/jats:styled-content><jats:sub>a<\/jats:sub>channel\u2010mediated vasodilation, through a mechanism independent of \u03b22\u2010<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>antagonistic or inverse agonistic action. Instead, the enhancement of acetylcholine relaxation seems likely to occur by a mechanism secondary to endothelial calcium increase.<\/jats:p>","DOI":"10.1111\/bcpt.12949","type":"journal-article","created":{"date-parts":[[2017,12,26]],"date-time":"2017-12-26T14:52:43Z","timestamp":1514299963000},"page":"570-576","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["\u03b2\u2010adrenergic Receptor Blocker<scp>ICI<\/scp>118,551 Selectively Increases Intermediate\u2010Conductance Calcium\u2010Activated Potassium Channel (IK<sub>Ca<\/sub>)\u2010Mediated Relaxations in Rat Main Mesenteric Artery"],"prefix":"10.1111","volume":"122","author":[{"given":"Melike Hacer","family":"Ozkan","sequence":"first","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy Hacettepe University Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serdar","family":"Uma","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy Hacettepe University Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00539.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/24388"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31828197bc"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000238377.08219.0c"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.150"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705421"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12121"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12160"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.11051"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091877"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.532960"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.5.4.893"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.130468"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3439fje"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2014.01.004"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431X20165285"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j..2003.t01-1-00801.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702616"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.262006"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.05.066"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.84947"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706369"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701546"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)00833-0"},{"key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S0022-3565(24)34971-7","article-title":"Heterogeneity of endothelium\u2010dependent vasodilation in pressurized cerebral and small mesenteric resistance arteries of the rat","volume":"290","author":"Lagaud GJ","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15908.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.172379"}],"container-title":["Basic &amp; 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