The present study investigated whether direct KATP activation induced angiogenic responses and whether it is required for the endothelial responses to C-type natriuretic peptide (CNP) or vascular endothelial growth factor (VEGF). In vivo, chick chorioallantoic membrane (CAM) angiogenesis was similarly enhanced by the direct KATP channel activator SG-209 (2-nicotinamidoethyl acetate) and by CNP. KATP inhibitors, glibenclamide and 5-hydroxydecanoate (5-HD), reduced basal and abolished CNP-induced CAM angiogenesis. In vitro, the direct KATP openers nicorandil and SG-209, and the polypeptides VEGF and CNP, increased proliferation and migration in bEnd.3 mouse endothelial cells. In addition, VEGF and CNP induced cord-like formation on Matrigel by human umbilical vein endothelial cells. All these in vitro endothelial responses were effectively abrogated by glibenclamide or 5-HD. These results demonstrate that direct pharmacological activation of KATP induces angiogenic effects, and that angiogenic responses to CNP and VEGF depend on KATP activation.
See article at J Pharmacol Exp Ther 2015, 354:79–87.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics