Abstract

Norepinephrine, a natural transmitter, is stored in vesicles of sympathetic nerve endings. Small amounts of this amine are released continuously into the circulation to maintain tonic activity; increasing amounts are released in response to sympathetic nerve stimulation. Cardiac catecholamine concentrations remained unaltered even in the face of vigorous sympathetic activity produced by 1) prolonged sympathetic nerve stimulation, 2) exposure to cold for 6 hr and 3) administration of histamine or β-tetrahydronaphthylamine. Such maintenance of endogenous amine levels was not possible when synthesis of norepinephrine was inhibited by the tyrosine hydroxylase inhibitor, α-methyltyrosine. In this case tissue catecholamine levels were reduced. This reduction, however, was antagonized by pretreatment of animals with ganglionic blocking agents, adrenergic neuron blocking agents or monoamine oxidase inhibitors or by destruction of the brain and spinal cord. The usual elevation in catecholamine levels after inhibition of monoamine oxidase or ganglionic blockade was not observed when synthesis was inhibited by α-methyltyrosine. The common factor in all these experiments is the inhibition of spontaneous release due to tonic impulses in sympathetic nerve fibers. This suggests that once synthesis is inhibited, tonic release of catecholamine is sufficient to cause a gradual depletion of the amine. This depletion after α-methyltyrosine was increased when sympathetic nerve activity was increased by various procedures. Since α-methyltyrosine did not affect the accumulation of H³-norepinephrine in the rat heart, these findings suggest that catecholamine synthesis is indeed increased in response to increased sympathetic nerve activity which helps to maintain normal levels of tissue catscholamine. Thus the present study shows that maintenance of endogenous amine levels is based largely on adjustment of local norepinephrine synthesis which is presumably regulated by activity in the sympathetic nerves.