Effects of Qibaipingfei capsules on pulmonary vascular relaxation through KATP channel activation by the NO cGMP signaling pathway

ABSTRACT

This research explores the effects of Qibaipingfei [QBPF] capsules on pulmonary vascular relaxation in vitro and the relationship of the ATP-sensitive K+ [KATP] channel and nitric oxide [NO] pathway. Vasodilator effects of QBPF [0.125-2 g/kg] on rat pulmonary artery rings were observed using a multi-wire myograph system. The maximum relaxation [Emax] of QBPF was detected following treatment involving endothelial denudation, N omega-nitro-L-arginine methyl ester [L-NAME], 1H-[1,2,4] oxadiazolo[4,3-alpha]quinoxalin-1-one [ODQ], or glyburide [GLYB]. Furthermore, rat models of phlegm and blood stasis syndrome combined with chronic obstructive pulmonary disease [COPD] were established using compound factors. KIR6.1 and SUR2B protein expression was analyzed by western blotting. After 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandinF2alpha [U46619] was used to pre-constrict endothelium-intact pulmonary artery rings, QBPF induced the effects of concentration-dependent relaxation at a concentration for 50% of maximal effect [EC50] of 0.56 g/L and Emax of 84.30% +/- 6.27%. After the endothelium was denuded, the vasodilator effects reduced significantly [P<0.01]. QBPF-induced relaxation was inhibited by L-NAME, ODQ, and GLYB [P<0.01]. The vasodilator effect was also attenuated in the model group [Emax=62.63% +/- 10.02, EC50 = 0.72 g/L, P<0.01]. In comparison with expression in the control group, SUR2B protein expression was down-regulated in the model group [P<0.01] but no significant difference was detected in KIR6.1 protein expression between the groups [P>0.05]. QBPF and nicorandil [Nic] treatment up-regulated SUR2B KATP channel expression [P<0.05]. QBPF induces endothelial-dependent relaxation in pulmonary artery rings in vitro, through a mechanism that potentially activates the KATP channel in pulmonary vascular smooth muscles via the NO-cyclic GMP [cGMP]-dependent pathway