Cardiovascular effects of Y-27632, a selective Rho-associated kinase inhibitor, assessed in the halothane-anesthetized canine model

Y-27632, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate, is a selective Rho-associated kinase inhibitor, which has been suggested to possess multiple clinical applications based on the in vitro observations. Since information regarding in vivo cardiovascular effects of Y-27632 is still limited, we assessed them using the halothane-anesthetized, closed-chest canine model. Administration of Y-27632 in a dose of 0.01 mg/kg, i.v. significantly decreased total peripheral vascular resistance together with an increase of cardiac output without affecting other cardiovascular parameters. Moreover, additional administration of Y-27632 in a dose of 0.1 mg/kg, i.v. significantly decreased blood pressure and left ventricular end-diastolic pressure, increased the heart rate and cardiac contractility, enhanced atrioventricular conduction and shortened the repolarization process as well as the effective refractory period. These results indicate that Y-27632 exerts a potent arterio-venodilator action with cardiostimulatory effects possibly through the sympathetic reflex in the in vivo canine model. (C) 2002 Elsevier Science B.V. All rights reserved.