Effects of amrinone on contractile activities, cyclic nucleotides and adenyl cyclase activity of cultured rat heart cells

Amrinone (Amr, 50 μmol/L) and isoprenaline (0.5 μmol/L) stimulated beating rate (BR) and contractile velocity (dV/dt) in cultured rat heart cells. Both dV/dt and BR were attenuated after exposing the cells to verapamil (10 nmol/L), Mn2+ (50 μmol/L) or low Ca2+ (0.6 mmol/L) medium. Amr (50 μmol/L) increased dV/dt in all treatments except verapamil (100 nmol/L). Intracellular cAMP levels, but neither cGMP nor adenyl cyclase activities, of cultured rat heart cells were increased by Amr 0.2 and 1.0 mmol/L. The effect of Amr on increasing cAMP level was neither potentiated by theophylling 0.5 mmol/L nor abolished by timolol l0 μmol/L. However, timolol 10 μmol/L blocked the effect of isoproterenol 50 μmol/L on elevating cellular cAMP level and adenyl cyclase activity. These results suggest that the enhancement of slow Ca2+ flow and inhibition of phosphodiesterase caused the positive inotropic effect of amrinone.