Abstract
AbstractThe purpose of the present study was to evaluate the pharmacological characteristics of the novel antihypertensive drug iptakalim hydrochloride and to investigate the molecular mechanisms underlying its antihypertensive action. In conscious hypertensive animals, oral administration of iptakalim hydrochloride at doses of 0.75, 1.5, 3.0, and 6.0 mg/kg in spontaneously hypertensive rats, or at doses of 0.125, 0.25, 0.5, and 1.0 mg/kg in renal hypertensive dogs (two‐kidney with one‐clip), decreased the blood pressure in a dose‐dependent manner. In conscious normotensive dogs blood pressure was not changed when iptakalim hydrochloride was given at doses of 0.8–3.2 mg/kg, but was decreased by 20 mmHg at the high dose of 12.8 mg/kg. Repeated administration of iptakalim hydrochloride decreased blood pressure in a dose‐dependent manner and also reversed the hypertensive cardiovascular remodeling. The molecular mechanisms underlying its antihypertensive action include ATP‐sensitive potassium channel activation and endothelin antagonism. Drug. Dev. Res. 58:65–68, 2003. © 2003 Wiley‐Liss, Inc.
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