Restriction of beta-adrenergic responsiveness in hypertrophied hearts of chronically isoproterenol-treated rats.

A single subcutaneous dose (1 mg/kg) of isoproterenol (ISO) increases the net calcium-45 uptake into the ventricular myocardium of normal rats by a factor of 3 to 4 within 6 hr. When the same dose of ISO was administered to rats previously treated with 1 mg ISO/kg per day for 1--3 weeks, this rise in labeled Ca-uptake was greatly reduced. Consequently the stimulatory effect of ISO on the Ca-dependent high-energy phosphate consumption was considerably diminished. Furthermore the chronic application of ISO produced a hypertrophy of both ventricles. When this treatment was discontinued for 7 days the ventricular weights returned to normal, whereas the restriction of beta-adrenergic reactivity persisted for more than 3 weeks. The results indicate that the decrease in responsiveness to beta-adrenergic agents is not due to the hypertrophy itself but must be considered to be an independent phenomenon-possibly resulting from adaptation to chronic beta-adrenergic overstimulation.