[Effects of iptkalim, a novel ATP-sensitive potassium channel opener, on hypoxia-induced pulmonary vascular remodeling in rats]

To investigate whether pulmonary vascular remodeling in hypoxic pulmonary hypertensive rats could be prevented by treatment with a selective K(ATP)CO, iptkalim (Ipt).Rats were fed in hypoxic and normobaric environment (10% +/- 0.5% O2, 8 h/day and 6 day/week) and divided into control group, hypoxia group (hypoxic rat treated with ig NS 5.0 ml x kg(-1) x d(-1)), treated group I (hypoxic rat treated with ig Ipt 0.75 mg x kg(-1) x d(-1)), treated group II (hypoxic rat treated with ig Ipt 1.5 mg x kg(-1) x d(-1)). After 4 wk, the mean pulmonary arterial pressure (mPAP), right ventricle/left ventricle and septum [RV/(LV + S)] were measured, and the small pulmonary arterial morphologic changes were observed with morphometric analysis under microscopes in four groups.The level of mPAP and RV/(LV+ S) was significantly higher in the hypoxic group than those in control group (P0.01). Morphometric analysis revealed that the ratio of vascular medial wall thickness to external diameter (MT%) and the ratio of vascular medial cross-sectional area to total arterial cross-sectional area (MA%) were also significantly increased in the hypoxic group than those in control group (P0.01) and the ratio of vessel lumen cross-sectional area to total arterial cross-sectional area (VA%) was significantly lower in the hypoxic group than those in control group (P0.01). Ipt 0.75 mg x kg(-1) x d(-1) or 1.5 mg x kg(-1) x d(-1) decreased the level of mPAP(mmHg), RV/(LV+ S), and inhibited the small pulmonary arterial remodeling significantly. Ipt 1.5 mg x kg(-1) x d(-1) reversed all pathological indices.K(ATP)CO iptkalim can be a very promising candidate for the treatment of hypoxic pulmonary hypertension.