Influence of lithium on the positive inotropic effect of phenylephrine and isoprenaline in guinea-pig heart.

The influence of lithium on the positive inotropic effects mediated by alpha- and beta-adrenoceptor stimulation was studied in isolated guinea-pig ventricular preparations stimulated at 1 Hz. Lithium chloride (10(-3)-2 X 10(-2) M) shifted the concentration-response curve for the inotropic effect of phenylephrine to the right in a dose-dependent manner. [3H]Prazosin binding was not inhibited by 10(-2) M lithium. The antagonistic effect of lithium was almost completely prevented by the presence of 10(-2) M myoinositol, and was potentiated by 10(-4) M 2-2'-anhydro-2-C-(hydroxymethyl)-myo-inositol, an antagonist of myo-inositol. The positive inotropic effect of isoprenaline was completely unaffected by either 10(-2) M lithium, 10(-2) M myo-inositol, or 10(-4) M 2-2'-anhydro-2-C-(hydroxymethyl)-myo-inositol. Since it is known that lithium interferes with inositol phosphate metabolism, our results produce further indirect evidence of an involvement of inositol phosphates in the myocardial response to alpha-adrenoceptor, but not to beta-adrenoceptor, stimulation. Our findings also suggest that chronic lithium treatment could interfere with the adrenergic modulation of myocardial contractility in those physio-pathological conditions in which the role of myocardial alpha-adrenoceptors becomes predominant.