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Iptakalim prevents rat pulmonary hypertension induced by endothelin‐1 through the activation of K ATP channel in vivo
Author(s) -
Wang Hong,
Xie Weiping,
Zhang Zheng,
Wang Hai,
Hu Gang,
Zhang Shijiang
Publication year - 2008
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20231
Subject(s) - glibenclamide , pulmonary hypertension , in vivo , pulmonary artery , pharmacology , potassium channel , endothelin 1 , ex vivo , medicine , chemistry , cardiology , endocrinology , receptor , biology , microbiology and biotechnology , diabetes mellitus
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 K ATP 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 µg/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 K ATP 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. Drug Dev Res 69: 89–94, 2008. © 2008 Wiley‐Liss, Inc.