The selective dilatation effects of iptakalim on pulmonary arterioles in hypoxic pulmonary hypertensive rat

Objective: To study the selective dilatation effects of iptakalim(Ipt),a novel ATP-sensitive potassium channel opener,on pulmonary arterioles in hypoxic pulmonary hypertensive rat.Methods: SD male rats were divided into 3 groups,control group,the rest were fed in hypoxic and normobaric environment(O2 10%±0.5%,8 h/d and 6 d/week) and divided into hypoxia group and hypoxia plus acetazolamide(Acz) group(hypoxic rats were treated with ig acetazolamide(Acz) 80 mg·kg-1·d-1).After 12 weeks,pulmonary arteriole rings about(197±4)μm were isolated and the tension of hypoxic pulmonary arterioles pre-contracted by 6 nmol/L endothelin-1(ET-1) was observed with wire myograph system model(DMT 610 m).The relaxing response of hypoxic pulmonary arterioles induced by different concentration of Ipt were detected and endothelial activity was also tested by acetylcholine.Results: 10-5 mol/L acetylcholine(ACh)-mediated vasodilatation was greatly reduced in the hypoxic group than those in control group(P0.01) and there was no significant difference between Acz treatment group and control group(P0.05).Ipt at the concentration ranging from 10-11 mol/L to 10-4 mol/L,caused dose dependent vasodilation on both hypoxic pulmonary arterioles and Acz treatment group(P0.05),but not on normal group.Conclusion: The endothelial function of pulmonary arterioles was damaged under hypoxic pulmonary hypertensive state,and Ipt showed selective dilatation effects on hypoxic pulmonary arterioles.Acz could improve the dysfunction of endothelial cells induced by hypoxic pulmonary hypertensive state,which didn't affect the selective dilatation effects of Ipt on hypoxic pulmonary arterioles.