AUTHOR=Zhang Danfeng , Krause Bernhard M. , Schmalz Hans-Günther , Wohlfart Paulus , Yard Benito A. , Schubert Rudolf 

TITLE=ET-CORM Mediated Vasorelaxation of Small Mesenteric Arteries: Involvement of Kv7 Potassium Channels

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.702392

DOI=10.3389/fphar.2021.702392

ISSN=1663-9812

ABSTRACT=<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<sup>+</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 (<italic>rac</italic>-<bold>1</bold> and <italic>rac</italic>-<bold>4</bold>) or pivalate (<italic>rac</italic>-<bold>8</bold>) as ester functionality, were tested <italic>ex vivo</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 (<italic>rac</italic>-<bold>1</bold> and <italic>rac</italic>-<bold>4</bold>), while treatment with the pivalate containing ET-CORM (<italic>rac</italic>-<bold>8</bold>) resulted in no vasodilation. Pre-treatment of mesenteric arteries with the sGC inhibitor ODQ abolished <italic>rac</italic>-<bold>4</bold> mediated vasodilation, similar as for the known sGC activator SNP. Likewise, <italic>rac</italic>-<bold>4</bold> mediated vasodilation did not occur in KCL pretreated mesenteric arteries. Although mesenteric arteries abundantly expressed a variety of K<sup>+</sup>-channels only Kv7 channels were found to be of functional relevance for <italic>rac</italic>-<bold>4</bold> mediated vasodilation. In conclusion the current results identified Kv7 channels as the main channel by which <italic>rac</italic>-<bold>4</bold> mediates vasodilation. In keeping with the central role of Kv7 in the control of vascular tone and peripheral resistance these promising <italic>ex-vivo</italic> data warrant further <italic>in vivo</italic> studies, particularly in models of primary hypertension or cardiac diseases, to assess the potential use of ET-CORMs in these diseases.</p>