The molecular pathway of ATP-sensitive potassium channel in endothelial cells for mediating arteriole relaxation

The endothelial molecular pathway of a new ATP-sensitive potassium channel (KATP) opener natakalim was investigated in mesenteric arterioles of rats. A DMT wire myograph was used to evaluate the vasorelaxation effects of natakalim. Ca2+ responses of endothelial cells induced by natakalim were measured by laser confocal fluorescence microscopy. NO assay kits and Western blotting were used. The new KATP opener natakalim significantly produced endothelium-dependent arteriolar dilation and increased endothelial cell intracellular calcium concentration ([Ca2+]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 Ca2+ influx induced by natakalim. These results suggest that endothelial KATP mediated natakalim-induced vasorelaxation through increasing [Ca2+]i and NO production. Activation of endothelial TRPV1 channels and subsequent Ca2+ entry, and NO release at least partly contribute to endothelium-dependent vasorelaxation induced by natakalim. [Display omitted]