Comparison of the electromechanical responsiveness of alpha-1-adrenoceptor stimulation in ventricles of normal and cardiomyopathic hamsters.
Alterations in alpha(1)-adrenoceptor (alpha(1)AR) density and related signal transduction proteins were reported in cardiomyopathic hearts in the failing stage. The electromechanical modification of alpha(1)-adrenergic stimulation in the failing heart is unclear. The present study compares the alpha(1)AR-stimulated electromechanical response in failing ventricles of genetically 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 with a transducer. In the presence of propranolol, phenylephrine increased the contraction and prolonged the action potential duration (APD) to similar values in ventricles of both strains, despite a prolonged basal APD in cardiomyopathic 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 significantly greater than that in BIO 14.6 hamsters. The effects of phenylephrine on the ventricular force-frequency relationship and on the mechanical restitution in both normal and BIO 14.6 strain hamsters were examined. The uniform negative force-frequency relationship and the altered mechanical restitution reveal a defect of intracellular Ca(2+) handling in cardiomyopathic BIO 14.6 hamsters. alpha(1)-Adrenergic modulation cannot convert the defective properties in the model of the failing heart. Nevertheless, phenylephrine decreased post-rest 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 Ca(2+) from the sarcoplasmic reticulum, although its action in prolonging the APD can indirectly increase the influx of Ca(2+).
Chen
W P
WP
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Su
M J
MJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D018663:Adrenergic Agents / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000503:physiopathology*; D006224:Cricetinae; D004347:Drug Interactions; D004594:Electrophysiology; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D023421:Models, Animal; D010656:Phenylephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology
D018663:Adrenergic Agents; D058646:Adrenergic alpha-1 Receptor Agonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate; D011433:Propranolol; D019311:Staurosporine; D002118:Calcium