Effects of iptakalim hydrochloride, a novel KATP channel opener, on pulmonary vascular remodeling in hypoxic rats.
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 KATPCO, 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 KATPCOs might be promising in the treatment of patients with hypoxic, and even possibly other forms of, pulmonary hypertension.
Xie
Weiping
W
Department of Pharmacology and Neurobiology, Nanjing Medical University,140 Hanzhong Road, 210029, China.
Wang
Hong
H
Wang
Hai
H
Hu
Gang
G
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology*; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D015221:Potassium Channels