Mechanism of the vasodilator effects of the cardiotonic agent DPI 201-106.
DPI 201-106 (DP) is a new cardiotonic agent. In experiment 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.
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002415:Cats; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D014665:Vasodilator Agents
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D009467:Neuromuscular Depolarizing Agents; D010879:Piperazines; D014665:Vasodilator Agents; D011189:Potassium Chloride; C046261:DPI 201-106; D002118:Calcium