Mechanism of the Vasodilator Effects of the Cardiotonic Agent DPI 201-106

Abstract

Summary: DPI 201-106 (DPI) is a new cardiotonic agent. In experiments on cats anaesthetized with chloralose/urethane, it lowered blood pressure and caused peripheral vasodilatation at doses between 0.3 and 3 mg/kg, infused i.v. Furthermore, DPI lowered heart rate and increased coronary blood flow (measured with tracer microspheres). The mechanism of this vasodilator action was investigated in experiments in vitro using rabbit aorta. DPI inhibited depolarization-induced contraction. The effect was strongly dependent on the contact time. The pIC₅₀ (−log IC₅₀) values for 15 min, 1, and 2 h pretreatment were 4, 5.2, and 5.7, respectively. ⁴⁵Ca²⁺ uptake into rabbit aorta was inhibited by DPI with pIC₅₀ values of 4.3, 5.1, and 5.7, respectively, for the pretreatment periods indicated above. The excellent agreement between effects on tension development and calcium uptake suggests that the mechanism of vasodilatation observed in vivo is related to calcium antagonism.