Evidence for α1-Adrenoceptor-Mediated Increase of Inositol Trisphosphate in the Human Heart

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Abstract
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 .mu.mol/L), maximally, to about 235% of control (at 100 .mu.mol/L). The inositol phosphates were increased t o195-262%, 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.