Time course of development and cessation of myocardial sensitization to isoproterenol by DCA-saline in the albino rat. The role of protein synthesis.

The time course the development of myocardial sensitization to isoproterenol induced by desoxycorticosterone acetate (DCA) was determined in albino rats implanted subcutaneously with various doses of DCA and maintained on 1% saline as drinking fluid. The animals were challenged at predetermined intervals following DCA implantation with a single, subcutaneous dose of isoproterenol (150 ug/kg body weight). The onset of myocardial sensitization, as determined by the incidence of mortality (due to ventricular fibrillation) was not dependent on the dose of DCA used and was noted within one or two days from the beginning of exposure to DCA. Removal of the steroid pellet after 6 days of pretreatment resulted in rapid decline of sensitization. Removal of DCA after 33 or 90 days of pretreatment, on the other hand, did not completely abolish sensitization. Treatment with the protein synthesis inhibitors cycloheximide and actinomycin D prevented the development of myocardial sensitization.