Study of the relationship between the neurotransmitter store and adrenergic nerve block induced by reserpine and guanethidine.

• It is now established that the administration of reserpine or guanethidine is capable of preventing the response of effector organs to direct stimulation of post-ganglionic sympathetic nerves,even though the effector organ system remains responsive to the administration of the adrenergic transmitter, norepinephrine.' 3 Since both of these drugs have been shown to be capable of producing depletion of the tissue contents of norepinephrine,' 5 it has been suggested that depletion of the adrenergic transmitter store is the fundamental mechanism by which reserpine and guanethidine block adrenergic transmission.' 6 However, McCubbin and associates have suggested, and Cass and Spriggs have offered strong indirect evidence to support the view that guanethidine blocks adrenergic transmission before it produces measurable tissue norepinephrine depletion. No information is available on the relationship between the degree of blockade to sympathetic stimulation produced by reserpine, and the concentration of the adrenergic transmitter in the nerve endings at the time of adrenergic nerve blockade. It was the objective of the experiments described in this report to compare the mechanisms of the adrenergic blockade induced by reserpine and guanethidine. Particular attention was directed toward establishing a quantitative relationship between the size of the store of sympathetic transmitter, as reflected in the myocardial content of norepinephrine, and the degree of adrenergic nerve blockade produced by these two drugs.