Cardiac effects of isoliquiritigenin

The effects of isoliquiritigenin on force of contraction (F-c), L-type Ca2+ current (I-CA) and intracellular Ca2+ concentration ([Ca2+](i)) were investigated in rat ventricular heart muscle. Isoliquiritigenin increased F-c and I-Ca and, after longer exposure times, resting tension and [Ca2+](i). The effect of isoliquiritigenin (100 mu M) on I-Ca was diminished by Rp-cAMPS (30 mu M). 1H-[1,2,4]oxa-diazolo[4,3-a]quinoxalin-1-one (50 mu M) did not influence the effects of isoliquiritigenin on F-c and I-Ca. The positive inotropic effects of isoprenaline and forskolin, but not of 3-isobutyl-1-methylxanthine, were potentiated by isoliquiritigenin (100 mu M). In the presence of milrinone (10 mu M), no further effects of isoliquiritigenin (100 mu M) on F-c and I-Ca were observed. It is suggested that the increase in F-c and I-Ca by isoliquiritigenin is due to an accumulation of cyclic AMP. These effects are probably unrelated to an effect of the drug on soluble guanylyl cyclase, as reported for smooth muscle, but rather due to a direct inhibition of phosphodiesterase III activity.