Prolonged treatment with isoproterenol causes a loss of myocardial Gsalpha mRNA expression

We investigated the influence of chronic beta-adrenergic stimulation on Gsalpha protein gene expression and beta-adrenoceptor responsiveness in rat ventricular myocardium. The rats received twice-daily injections of 4 mg/kg isoproterenol (ISO) alone or with 8 mg/kg propranolol (PROP) for 4 days. In ventricular myocardium, Gsalpha mRNA expression decreased by 27% after ISO treatment. Dose-dependent (10 nM to 100 micro M) positive inotropic responses by ISO in the left papillary muscles were lower after ISO treatment than in saline-treated myocardium with decreases in ED50 values. PROP itself had no effect, although it antagonized both ISO-induced effects. These results suggest that impaired Galpha mRNA expression may explain the loss of cardiac Gsalpha subunit levels after chronic beta-adrenergic stimulation, and that these changes can provide one mechanism for the progress of long-term desensitization.