Ability of vasoconstrictor drugs to cause adrenal medullary discharge after "sensitization" by ganglion stimulating agents.

Abstract

Administration of 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) subcutaneously, intravenously or into a lurnboadrenal artery for 20, or more, minutes in dosages that caused little, or no, change in arterial pressure caused the adrenal glands to respond to intravenous or local intra-arterial injection of vasoconstrictor drugs (angiotensin, norepi-nephrine, serotonin, vasopressin, phenyleph-rine, metaraminol, or barium chloride) by discharging large amounts of pressor material. Nicotine and tetramethylamnionium chloride given into a lumboadrenal artery had the same sensitizing effect; prolonged electrical stimulation of the cut peripheral end of the thoracic or lumbar sympathetic trunk or splanchnic nerve did not. Sensitization persisted during infusions or for at least one hour after subcutaneous administration of a ganglion stimulating agent. As after intravenous injection of a pressor drug, adrenal discharge caused reflex decrease of efferent sympathetic nerve activity. Following sensitization, partial constriction of a lumboadrenal artery proximal to the adrenal, or injection of potassium cyanide into the artery, produced responses comparable to those elicited by injection of vasoconstrictor drugs; carotid occlusion or electrical stimulation of the cut peripheral end of a splanchnic nerve did not cause the same large adrenal discharge. Partial constriction of the adrenal artery, or drug injection, did not cause adrenal discharge prior to administration of a ganglion stimulating agent. Discharge due to intra-arterial injection of a vasoconstrictor drug was prevented by simultaneous infusion of a vasodilator drug, sodium nitroprusside, into the adrenal artery. The sensitizing effect of the ganglion stimulating drugs was not prevented by atro-pine, ergotamine, spinal cord section at C6, splanchnic nerve section, or establishment of tachyphylaxis to vasopressin. It was eliminated for prolonged periods by injection of very small dosage of tetraethylammonium chloride or phentolamine into the adrenal artery. It is concluded tentatively that ganglion stimulating agents cause sensitization of receptors in, or near, the adrenal glands which, through a local neural mechanism containing a cholinergic synapse and an adrenergic receptor, respond to hypoxia by causing discharge of catechol amines.