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Published on: September 14, 2012
The molecular pathway of ATP-sensitive potassium channel in endothelial cells for mediating arteriole relaxation
Xuejun Chen1, Wenzhi Han1, Yanfang Zhang1
1Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
Aims:
The endothelial molecular pathway of a new ATP-sensitive potassium channel (KATP) opener natakalim was investigated in mesenteric arterioles of rats.
Main Methods:
A DMT wire myograph was used to evaluate the vasorelaxation effects of natakalim. Ca(2+) responses of endothelial cells induced by natakalim were measured by laser confocal fluorescence microscopy. NO assay kits and Western blotting were used.
Key Findings:
The new KATP opener natakalim significantly produced endothelium-dependent arteriolar dilation and increased endothelial cell intracellular calcium concentration ([Ca(2+)]i) as well as NO release, which could be inhibited by SB366791 and capsazepine, the specific TRPV1 blockers. Additionally, down-regulation of endothelial TRPV1 by RNA interference inhibited the Ca(2+) influx induced by natakalim.
Significance:
These results suggest that endothelial KATP mediated natakalim-induced vasorelaxation through increasing [Ca(2+)]i and NO production. Activation of endothelial TRPV1 channels and subsequent Ca(2+) entry, and NO release at least partly contribute to endothelium-dependent vasorelaxation induced by natakalim.
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