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.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D007545:Isoproterenol; D002118:Calcium