Comparison of the electromechanical responsiveness of alpha-1-adrenoceptorstimulation in ventricles of normal and cardiomyopathic hamsters

Alterations in alpha (1)-adrenoceptor (alpha (1)AR) density and related sig nal transduction proteins were reported in cardiomyopathic hearts in the fa iling stage. The electromechanical modification of alpha (1)-adrenergic sti mulation in the failing heart is unclear. The present study compares the al pha (1)AR-stimulated electromechanical response in failing ventricles of ge netically cardiomyopathic BIO 14.6 hamsters (280-320 days old) with that in age-matched normal Syrian hamsters. The action potential was recorded with a conventional microelectrode technique, and twitch force was measured wit h a transducer. In the presence of propranolol, phenylephrine increased the contraction and prolonged the action potential duration (APD) to similar v alues in ventricles of both strains, despite a prolonged basal APD in cardi ormyopathic ventricles. The positive inotropism stimulated by phenylephrine was inhibited by staurosporine, and was potentiated by 4 beta -phorbol-12, 13-dibutyrate (PDBu) in both strains. The maximum positive inotropic effect of phenylephrine in PDBu-treated ventricles of normal hamsters was signifi cantly greater than that in BIO 14.6 hamsters. The effects of phenylephrine on the ventricular force-frequency relationship and on the mechanical rest itution in both nor-mall and BIO 14.6 strain hamsters were examined. The un iform negative force-frequency relationship and the altered mechanical rest itution reveal a defect of intracellular Ca2+ handling in cardiomyopathic B IO 14.6 hamsters. alpha (1)-Adrenergic modulation cannot convert the defect ive properties in the model of the failing heart. Nevertheless, phenylephri ne decreased postrest potentiation in short rest periods, and enhanced post rest decay after longer resting periods. The results indicate that alpha (1 -)adrenergic action enhances a gradual loss of Ca2+ from the sarcoplasmic r eticulum, although its action in prolonging the APD can indirectly increase the influx of Ca2+. Copyright (C) 2001 National Science Council, ROC and S . Karger AG, Basel.