Effect of an antihypertensive hydrazine derivative on Ca 2+ current of single frog cardiac cells

Abstract

The effects of MP 518, an acylated 2-chlorobenzylidene hydrazidone derivative with antihypertensive properties were investigated on the Ca current, I Ca, recorded under whole-cell patch-clamp in single frog ventricular cells. MP 518 (1–100 μM) had no effect on I Ca under control conditions. However, at 10 μM it significantly increased the β-adrenergic stimulated I Ca, an effect similar to that of isobutylmethyl-xanthine (IBMX), a non-specific phosphodiesterase inhibitor. The effects of MP 518 and IBMX were not, however, additive. This positive effect was also observed with both compounds, MP 518 and IBMX, when a submaximal dose of cyclic AMP was intracellularly perfused. In the presence of IBMX or at a high concentration (100 μM), MP 518 had a negative effect on β-adrenergic stimulated I Ca. It was thus considered that the main effect of MP 518 is an antiphosphodiesterase activity, since the increase in I Ca induced by low concentrations of MP 518 could be related to inhibition of cAMP degradation; however, at higher concentrations, MP 518 antagonizes β-adrenergic stimulation, possibly at several levels. Such an antiphosphodiesterase activity can account for the vasorelaxant effects as well as the tachycardic effects of MP 518.