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• W3197756162 abstract "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 + -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 ( rac - 1 and rac - 4 ) or pivalate ( rac - 8 ) as ester functionality, were tested ex vivo 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 ( rac - 1 and rac - 4 ), while treatment with the pivalate containing ET-CORM ( rac - 8 ) resulted in no vasodilation. Pre-treatment of mesenteric arteries with the sGC inhibitor ODQ abolished rac - 4 mediated vasodilation, similar as for the known sGC activator SNP. Likewise, rac - 4 mediated vasodilation did not occur in KCL pretreated mesenteric arteries. Although mesenteric arteries abundantly expressed a variety of K + -channels only Kv7 channels were found to be of functional relevance for rac - 4 mediated vasodilation. In conclusion the current results identified Kv7 channels as the main channel by which rac - 4 mediates vasodilation. In keeping with the central role of Kv7 in the control of vascular tone and peripheral resistance these promising ex-vivo data warrant further in vivo studies, particularly in models of primary hypertension or cardiac diseases, to assess the potential use of ET-CORMs in these diseases." @default.
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• W3197756162 date "2021-09-06" @default.
• W3197756162 modified "2023-10-14" @default.
• W3197756162 title "ET-CORM Mediated Vasorelaxation of Small Mesenteric Arteries: Involvement of Kv7 Potassium Channels" @default.
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• W3197756162 doi "https://doi.org/10.3389/fphar.2021.702392" @default.
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