Molecular of pulmonary arterioles relaxation through SUR2B/Kir6.1 channel opening

Abstract

To study the dilatation characteristics of ATP-sensitive potassium channel (KATP) SUR2B/Kir6.1 subtype opener iptakalim (Ipt) in pulmonary arterioles, and to explore its possible mechanism. Vessels pressure-diameter monitoring perfusion technique was used to observe the dilatation effects of Ipt in rats fourth pulmonary arterioles (n=6~8). After the pulmonary arterioles were pre-treated with removing endothelium or pre-incubated with KATP channel blocker glibenclamide (Gli), cyclo-oxygenase (COX) inhibitor indomethacin (Indo) and nitric oxide synthase (NOS) inhibitor L-Nω-Nitro-arginine methyl ester(L-NAME), the dilatation effects of Ipt were observed. Pulmonary arterioles could be relaxed by Ipt, the maximal relaxation rate was (60.53±2.08)%. Compaired with control group, the effects of Ipt in endothelium denuded arterioles were significantly decreased, the maximal relaxation rate was (9.47±1.56)% (P<0.01). The maximal relaxation rate were decreased to(17.49±1.47)%,(37.00±3.88)% and(24.91±2.30)% respectively after Gli,Indo,L-NAME were pre-incubated (P<0.01). Pulmonary arterioles can be relaxed by Ipt. The selective activation of KATP SUR2B/Kir6.1 subtype by Ipt was involved in its mechanisms. The endothelium-dependently dilatation of Ipt was related to nitric oxide (NO) and prostacyclin (PGI2) released by endothelial cells.