Abstract: AIM: To investigate the effects of iptakalim hydrochloride (IPT) on endothelin-1 (ET-1)-induced pulmonary hypertension in rats.METHODS: The effects of IPT administered by cumulative method on vasoconstriction mediated by ET-1 were studied with rings of pulmonary arteries isolated from normal rats.The rat model of pulmonary hypertension was prepared by injecting ET-1 through pulmonary artery.The mean pulmonary arterial pressure (mPAP), heart rate (HR), systemic blood pressure were monitored by polygraph.RESULTS: In vitro studies, IPT at the concentration of 0.05 to 50 nmol·L^-1antagonized vasoconstriction induced by ET-1 in a concentration-dependent manner.The IC₅₀ value for dilating PA rings-preconstricted with ET-1 was 5.84 nmol·L^-1.In vivo studies, ET-1 induced a significant increase in mPAP from 21.37±2.64 mmHg to 26.23±3.94 mmHg.Pulmonary artery pressure recovered 60 minutes after ET-1 infusion.Both IPT 1.0 and 0.5 mg·kg^-1could prevent the pulmonary hypertension induced by ET-1.The prevention of ET-1-induced pulmonary hypertension afforded by IPT 1.0mg·kg^-1was abolished by pretreatment of rats with the K_ATP channel inhibitors, glibenclimide (Gli).IPT of 1.0 mg·kg^-1blocked pulmonary hypertension induced by ET-1 10, 20 and 30 minutes after ET-1 infusion.But IPT 0.5 mg·kg^-1had no effect on pulmonary hypertension induced by ET-1. IPT 1.0 or 0.5 mg·kg^-1which was administered as a bolus infusion into pulmonary artery had no effect on normal pulmonary artery pressure.CONCLUSION: IPT of 1.0 mg·kg^-1can significantly treat and prevent the pulmonary hypertension induced by ET-1 through activating K_ATP channel without affecting normal pulmonary artery pressure.It is a promising candidate for the treatment of pulmonary hypertension.

Key words: pulmonary hypertension, ATP-sensitive potassium channel, endothelin-1, iptakalim hydrochloride