Iptakalim has been previously characterized as a novel, selective ATP-sensitive potassium channel opener. In the present study, to determine whether iptakalim can prevent the pulmonary hypertension induced by endothelin-1 (ET-1) through the activation of K-ATP channel in vivo, the effects of iptakalim and glibenclamide (a selective KATP channel blocker) on the mean pulmonary pressure (mPAP) induced by ET-1 were examined in rats. Treatment of the animals with exogenous ET-1 (via the pulmonary artery at a dose of 1.5 mu g/kg) induced a pulmonary hypertension in vivo, whereas the administration of iptakalim (via the pulmonary artery at doses of either 0.5 mg or 1.0 mg/kg) prior to ET-1 prevented pulmonary hypertension induced by ET-1 in vivo. The ability of iptakalim to prevent pulmonary hypertension induced by ET-1 was abolished by glibenclamide (via the femoral artery at a dose of 20 mg/kg) in vivo. These findings provide strong evidence that iptakalim acts as a specific KATP channel opener to antagonize the vasoconstrictor effect of ET-1 in the pulmonary circulation. Thus, iptakalim may be developed as a therapeutic option for the treatment of pulmonary hypertension.
