EFFECTS OF CHRONIC PRETREATMENT WITH SMALL DOSES OF RESERPINE UPON ADRENERGIC NERVE FUNCTION

¹ Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan

Effects of accelerans nerve stimulation on heart rate in open-chest guinea pigs and of field stimulation upon force of contraction of isolated left atrial strips were determined after pretreatment of guinea pigs with reserpine for 7 days. Dose-response relationships were determined for norepinephrine and tyramine upon rate of beating of right atria and upon force of contraction of isolated left atrial strips. Reserpine (1-100 µg/kg/24 hr) decreased norepinephrine content and the retention of ³H-norepinephrine in cardiac tissues. Right atria showed a 3-fold increase in sensitivity to norepinephrine after chronic reserpine pretreatment (100 µg/kg/24 hr), whereas isolated left atrial strips showed no change in sensitivity. After reserpine (30 and 100 µg/kg/24 hr), right atrial norepinephrine levels were reduced by 85%, but the frequency-response curves to accelerans nerve stimulation were shifted to the left. There were decreases in the maximum responses to field stimulation and to tyramine at these doses of reserpine. After reserpine (10 µg/kg/24 hr) for 7 days, left atrial norepinephrine content was reduced by 91%. Although maximum responses to tyramine were also decreased, there were no changes in the frequency-response curves for either accelerans nerve stimulation or field stimulation. This study indicates that the store of norepinepihrine necessarv for the normal function of adrenergic neurons during nerve stimulation is extremely small.

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