Effects of iptakalim hydrochloride, a novel K ATP channel opener, on pulmonary vascular remodeling in hypoxic rats

Abstract

To investigate whether pulmonary artery remodeling could be prevented or not in hypoxic pulmonary hypertensive rats by treatment, the effects of iptakalim hydrochloride, a novel K ATPCO, were evaluated. Iptakalim hydrochloride was orally administered at the doses of either 1.5 mg/kg/day or 0.75 mg/kg/day before their 4-week exposure to hypoxia (10% oxygen). It was demonstrated that iptakalim hydrochloride could reverse all pathological indices of pulmonary arterial remodeling and significantly reduce right ventricular hypertrophy in hypoxic rats. The reversal of hypoxic indices was dose-dependent, in which the higher dose of iptakalim hydrochloride reversed pathological indices more effectively than the lower dose did. This was further confirmed electrophysiologically using whole cell patch-clamp technique, which revealed that the outward potassium currents could be enhanced by iptakalim hydrochloride, and the decrease of K + current density and increase of membrane capacitance could be reversed by chronic iptakalim hydrochloride treatment. These findings implied that iptakalim hydrochloride could play its role through activating plasmalemmal K + channels of pulmonary arterial SMCs. The results indicated that iptakalim hydrochloride had anti-remodeling properties of pulmonary artery in hypoxic pulmonary hypertensive rats. It is therefore suggested that K ATPCOs might be promising in the treatment of patients with hypoxic, and even possibly other forms of, pulmonary hypertension.