Evidence for alpha 1-adrenoceptor-mediated increase of inositol trisphosphate in the human heart

In human-isolated ventricular myocardium the alpha 1-adrenoceptor agonist phenylephrine has a positive inotropic effect but its mechanism is largely unknown. We studied the effects of phenylephrine in trabeculae isolated from three nonfailing human hearts. We found that the force of contraction rose concentration-dependently (1-300 mumol/L), maximally, to about 235% of control (at 100 mumol/L). The inositol phosphates were increased to 195-262%, whereas the phosphatidylinositol phosphate and phosphatidylinositol bisphosphate decreased to 69-73% of control. The present results suggest that the alpha 1-adrenoceptor-mediated increase in inositol trisphosphate and the positive inotropic effect may be causally related in the normal human heart.