Cardiovascular Effects of L-158,809, a New Angiotensin Type 1 Receptor Antagonist, Assessed Using the Halothane-Anesthetized In Vivo Canine Model.

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Abstract

L-158,809 is a new angiotensin II type 1 receptor antagonist. We simultaneously assessed its antagonistic potency and cardiovascular effects with the halothane-anesthetized in vivo canine model (n = 5). L-158,809 was intravenously infused over 10 min at escalating doses of 0.03, 0.3 and 3 mg/kg. Angiotensin II (0.1 μg/kg, i.v.)-induced vasopressor and negative inotropic responses were significantly suppressed from the low dose L-158,809. Meanwhile, L-158,809 did not affect any of the cardiovascular parameters except that QTc was slightly shortened after the high dose administration. These results support the previous in vitro knowledge that L-158,809 is a highly selective angiotensin II receptor antagonist.

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