EFFECTS OF VESNARINONE (OPC-8212) ON CA2-ACTIVATED K-CHANNELS AND CYTOSOLIC CA2+ IN CULTURED SMOOTH-MUSCLE CELLS FROM PORCINE CORONARY-ARTERY()

Vesnarinone is a new, non vasodilating cardiotonic agent. This study c ompared the effects of vesnarinone and amrinone, a phosphodiesterase ( PDE) inhibitors with vasodilating actions, on cultured smooth muscle c ells from the porcine coronary artery. Application of vesnarinone (10( -4) M) or amrinone (10(-4) M) to the bath solution in cell-attached pa tches activated the K(Ca) channel having a conductance of 133 pS (bath 2.7 mM K, pipette 140 mM K). Application of vesnarinone to the cytoso lic side had no direct effect on K(Ca) channel activities in inside-ou t patches. Activation of the K(Ca) channel was suppressed when the int racellular production of cAMP was suppressed by preincubation with car bachol (10(-6) M). Amrinone, but not vesnarinone, lowered [Ca2+]i in t he K+-depolarized smooth muscle cells (K+ = 70 mM). These results sugg est that vesnarinone exerts an additional effect on [Ca2]i that is ind ependent of PDE inhibition. The difference in the effects on [Ca2+]i i n vascular smooth muscle cells may explain in part the differing actio ns of these agents on vascular relaxation.