Universität zu Köln

Zhang, Danfeng, Krause, Bernhard M., Schmalz, Hans-Gunther, Wohlfart, Paulus, Yard, Benito A. and Schubert, Rudolf (2021). ET-CORM Mediated Vasorelaxation of Small Mesenteric Arteries: Involvement of Kv7 Potassium Channels. Front. Pharmacol., 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1663-9812

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zhang, Danfeng UNSPECIFIED UNSPECIFIED UNSPECIFIED Krause, Bernhard M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmalz, Hans-Gunther UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohlfart, Paulus UNSPECIFIED UNSPECIFIED UNSPECIFIED Yard, Benito A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schubert, Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-590884
DOI:	10.3389/fphar.2021.702392
Journal or Publication Title:	Front. Pharmacol.
Volume:	12
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1663-9812
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CARBON-MONOXIDE SENSITIVITY; RAT SMALL ARTERIES; MOLECULE CORM-3; NITRIC-OXIDE; K+ CHANNELS; HEME; MECHANISMS; EXPRESSION; DYSFUNCTION; ACTIVATION Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59088