ET-CORM mediated vasorelaxation of small mesenteric arteries: involvement of Kv7 potassium channels
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...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
06 September 2021
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| In: |
Frontiers in pharmacology
Year: 2021, Volume: 12, Pages: 1-11 |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2021.702392 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fphar.2021.702392 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/article/10.3389/fphar.2021.702392 
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| Author Notes: | Danfeng Zhang, Bernhard M. Krause, Hans-Günther Schmalz, Paulus Wohlfart, Benito A. Yard and Rudolf Schubert |
| Summary: | 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. |
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| Item Description: | Gesehen am 26.10.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2021.702392 |