A new method of assessing adrenal medullary release utilizing the cardiovascular system of the rat

A new method of evoking and assessing adrenal medullary amine release has been developed utilizing pithed rats and whole left adrenal gland field stimulation. The stimulus-induced release was assessed by comparing the rise in systolic blood pressure with that evoked by intravenous epinephrine. The blood pressure response to field stimulation was biphasic, consisting of an initial, but variable neurogenic vasoconstrictor component, followed by a stable secondary component, attributable to medullary catecholamine release. Pharmacologic studies showed that both components were pre-synaptic in origin. The former phase involved acetylcholine release at the cardiac and coeliac ganglia followed by noradrenergic activation; the latter phase evoked acetylcholine release from extrinsic and/or intrinsic adrenal splanchnic nerve terminals, followed by medullary release. The initial component was shown not to quantitatively interfere with the response height of the secondary component, thus permitting use of the method for quantitative assessments. Medullary release proved to be very resistant to interference by drugs and pathological states. The acute (2-24 hour) administration of 6-hydroxydopamine, guanethidine and bethanidine, or the chronic administration of guanethidine (20 and 100 mg/kg, i.p. for 14 days) failed to alter medullary release. Similarly, hypophysectomy (30 days) appeared not to affect stimulus-induced release. Other than ganglion blocking agents, reserpine was the only drug which induced a depressed function. Thus the integrity of granular storage elements seems an essential prerequisite for release, whereas alterations in the activity of synthesizing and metabolizing enzymes (hypophysectomy and 6-hydroxydopamine) seems to be a relatively insignificant factor. Hypophysectomy exposed an inherent disadvantage of the technique since cardiovascular function was drastically impaired. Experiments made to elucidate this phenomenon indicated a depression of myocardial function but no vascular or adrenergic neuronal impairments were revealed. Hemodynamic depression following hypophysectomy was not due to adrenal steroid insufficiency as judged by studies in adrenal ectomi zed rats. The developed technique of assessing adrenal medullary release in vivo seems to be superior to pre-existing methods in the rat. However, its usefullness depends upon a responsive cardiovascular system for reliable assay purposes.