ENHANCED MYOCARDIAL-FUNCTION IN TRANSGENIC MICE OVEREXPRESSING THE BETA(2)-ADRENERGIC RECEPTOR

Transgenic mice were created with cardiac-specific overexpression of t he beta(2)-adrenergic receptor. This resulted in increased basal myoca rdial adenylyl cyclase activity, enhanced atrial contractility, and in creased left ventricular function in vivo; these parameters at baselin e in the transgenic animals were equal to those observed in control an imals maximally stimulated with isoproterenol. These results illustrat e a useful approach for studying the effect of gene expression on card iac contractility. Because oh ron ic heart failure in humans is accom panied by a reduction in the number of myocardial beta-adrenergic rece ptors and in inotropic responsiveness, these results suggest a potenti al gene therapy approach to this disease state.