Mechanisms in inhibitory action of aclarubicin on contractility of rat aorta.

The effects of aclarubicin on vasocontractile response and 45Ca2+ influx were investigated using rat isolated aorta. KCl-induced contractile force in medium containing 2 center dot 5 mM calcium and calcium-induced contractile force in high K+ (60 mM)-depolarized aorta were both markedly attenuated by aclarubicin (70 microM) pretreatment. 45Ca2+ influx stimulated by 60 mM KCl was significantly lower in the aclarubicin (70 microM)-pretreated aorta compared with the control. Aclarubicin pretreatment attenuated phorbol 12, 13-dibutyrate (1 microM)-induced contraction both in the presence and absence of calcium in the medium. Aclarubicin pretreatment also attenuated caffeine (20 mM)-induced transient contraction. These results suggest that aclarubicin attenuates vasoconstriction by inhibiting both Ca2+ entry through the voltage-dependent calcium channel and the intracellular contractile pathway after elevation of intracellular free calcium in vascular smooth muscle, in addition to the known mechanism of inhibition of phosphoinositides hydrolysis.