Norepinephrine depletion and sensitivity changes in rat heart induced by pretreatment with reserpine

Depletion of norepinephrine, sensitivity to isoproterenol and sensitivity to tyramine in rat atria were investigated after various doses and schedules of pretreatment of rats with reserpine. Virtually complete depletion of norepinephrine occurred in both right and left atria and ventricles after doses of 1.0 mg/kg/day of reserpine for one or more days of pretreatment. A smaller dose, 0.3 mg/kg/day, produced lesser depletion, and a larger dose, 2.5 mg/kg/day, caused severe central nervous system depression and high mortality. Chronic treatment (5 days or longer) with the 1.0-mg/kg/day dose produced supersensitivity of right atria to the chronotropic, but not inotropic, responses to isoproterenol. Chronic treatment with this dose for 7 days produced inotropic supersensitivity in left atria. Most of the schedules of pretreatment with reserpine depressed the maximum response to tyramine. However, the data indicate that the tyramine-releasable norepinephrine was not a consistent reflection of the total norepinephrine pool, even when depletion was very pronounced. The effects of depletion of cardiac stores of norepinephrine with reserpine in comparison with the effects of cardiac sympathectomy are discussed.