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Vesnarinone is a new, non vasodilating cardiotonic agent. This study compared the effects of vesnarinone and amrinone, a phosphodiesterase (PDE) inhibitors with vasodilating actions, on cultured smooth muscle cells from the porcine coronary artery. Application of vesnarinone (10(-4) M) or amrinone (10(-4) M) to the bath solution in cell-attached patches activated the KCa channel having a conductance of 133 pS (bath 2.7 mM K, pipette 140 mM K). Application of vesnarinone to the cytosolic side had no direct effect on KCa channel activities in inside-out patches. Activation of the KCa channel was suppressed when the intracellular production of cAMP was suppressed by preincubation with carbachol (10(-6) M). Amrinone, but not vesnarinone, lowered [Ca2+]i in the K(+)-depolarized smooth muscle cells (K+ = 70 mM). These results suggest that vesnarinone exerts an additional effect on [Ca2+]i that is independent of PDE inhibition. The difference in the effects on [Ca2+]i in vascular smooth muscle cells may explain in part the differing actions of these agents on vascular relaxation.

Effects of Vesnarinone (OPC-8212) on Ca2+-Activated K Channels and Cytosolic Ca2+ in Cultured Smooth Muscle Cells from Porcine Coronary Artery.