Study of the Relationship Between the Neurotransmitter Store and Adrenergic Nerve Block Induced by Reserpine and Guanethidine

The heart rate response to cardioaccelerator nerve stimulation and the corresponding levels of myocardial norepinephrine content were determined and correlated in dogs at various time intervals following the intravenous injection of either 3 mg/kg reserpine, or 10 mg/kg guanethidine. Guanethidine produced complete blockade of the cardiac accelerator response before producing measurable myocardial depletion of norepinephrine. In contrast, reserpine reduced the positive chronotropic response to cardioaccelerator nerve stimulation only after myocardial norepinephrine levels have been reduced to approximately 0.3 μg/g. An infusion of norepinephrine did not restore the heart rate response to cardioaccelerator nerve stimulation in either the reserpine or guanethidine treated dogs. These data suggest that the interference with adrenergic transmission produced by guanethidine is independent of changes in the level of stored adrenergic transmitter. The reserpine-induced blockade of adrenergic transmission may ultimately be dependent upon the mission may ultimately be dependent upon the depletion of adrenergic transmitter, but almost complete depletion of stored adrenergic transmitter must occur before reserpine-induced adrenergic blockade occurs.