Cardiac effects of a selective rho-associated kinase inhibitor, Y-27632, assessed in canine isolated, blood-perfused heart preparations.

Abstract

Chronotropic, inotropic and coronary effects of Y-27632 ((+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate), a specific inhibitor of Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK), were assessed using canine isolated, blood-perfused heart preparations. Y-27632 slightly enhanced sinoatrial automaticity and significantly increased coronary blood flow, while it decreased ventricular contraction. The concentrations of Y-27632 needed to cause the currently observed changes were similar to those inhibiting ROCK in a previous in vitro study. These results suggest that the constitutional ROCK in the heart mainly regulates the ventricular contractility and coronary vascular tone rather than the sinoatrial automaticity.