{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T03:43:58Z","timestamp":1774323838124,"version":"3.50.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Although the vasoactive properties of carbon monoxide (CO) have been extensively studied, the mechanism by which CO mediates vasodilation is not completely understood. Through-out published studies on CO mediated vasodilation there is inconsistency on the type of K<jats:sup>+<\/jats:sup>-channels that are activated by CO releasing molecules (CORMs). Since the vasorelaxation properties of enzyme triggered CORMs (ET-CORMs) have not been studied thus far, we first assessed if ET-CORMs can mediate vasodilation of small mesenteric arteries and subsequently addressed the role of soluble guanylate cyclase (sGC) and that of K-channels herein. To this end, 3 different types of ET-CORMs that either contain acetate (<jats:italic>rac<\/jats:italic>-<jats:bold>1<\/jats:bold> and <jats:italic>rac<\/jats:italic>-<jats:bold>4<\/jats:bold>) or pivalate (<jats:italic>rac<\/jats:italic>-<jats:bold>8<\/jats:bold>) as ester functionality, were tested <jats:italic>ex vivo<\/jats:italic> on methoxamine pre-contracted small rat mesenteric arteries in a myograph setting. Pre-contracted mesenteric arteries strongly dilated upon treatment with both types of acetate containing ET-CORMs (<jats:italic>rac<\/jats:italic>-<jats:bold>1<\/jats:bold> and <jats:italic>rac<\/jats:italic>-<jats:bold>4<\/jats:bold>), while treatment with the pivalate containing ET-CORM (<jats:italic>rac<\/jats:italic>-<jats:bold>8<\/jats:bold>) resulted in no vasodilation. Pre-treatment of mesenteric arteries with the sGC inhibitor ODQ abolished <jats:italic>rac<\/jats:italic>-<jats:bold>4<\/jats:bold> mediated vasodilation, similar as for the known sGC activator SNP. Likewise, <jats:italic>rac<\/jats:italic>-<jats:bold>4<\/jats:bold> mediated vasodilation did not occur in KCL pretreated mesenteric arteries. Although mesenteric arteries abundantly expressed a variety of K<jats:sup>+<\/jats:sup>-channels only Kv7 channels were found to be of functional relevance for <jats:italic>rac<\/jats:italic>-<jats:bold>4<\/jats:bold> mediated vasodilation. In conclusion the current results identified Kv7 channels as the main channel by which <jats:italic>rac<\/jats:italic>-<jats:bold>4<\/jats:bold> mediates vasodilation. In keeping with the central role of Kv7 in the control of vascular tone and peripheral resistance these promising <jats:italic>ex-vivo<\/jats:italic> data warrant further <jats:italic>in vivo<\/jats:italic> studies, particularly in models of primary hypertension or cardiac diseases, to assess the potential use of ET-CORMs in these diseases.<\/jats:p>","DOI":"10.3389\/fphar.2021.702392","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T17:56:13Z","timestamp":1630950973000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["ET-CORM Mediated Vasorelaxation of Small Mesenteric Arteries: Involvement of Kv7 Potassium Channels"],"prefix":"10.3389","volume":"12","author":[{"given":"Danfeng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard M.","family":"Krause","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-G\u00fcnther","family":"Schmalz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulus","family":"Wohlfart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benito A.","family":"Yard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf","family":"Schubert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1016\/j.jtcvs.2005.07.055","article-title":"The Induction of Heme Oxygenase 1 Decreases Contractility in Human Internal Thoracic Artery and Radial Artery Grafts","volume":"130","author":"Achouh","year":"2005","journal-title":"J. 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