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
-4M) or amrinone (10
-4M) to the bath solution in cell-attached patches activated the K
Ca channel having a conductance of 133 pS (bath 2.7mM K, pipette 140mM 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
-6M). Amrinone, but not vesnarinone, lowered [Ca
2+]i in the K
+-depolarized smooth muscle cells (K
+=70mM). These results suggest that vesnarinone exerts an additional effect on [Ca
2+]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.
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