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Epinephrine or isoproterenol was infused into a lateral tail vein of female Wistar rats under Nembutal anesthesia. After 20 min of diffusion, trunk blood was collected for the determination of plasma corticosterone (B) and ACTH immunoreactivity (ACTHi). Infusion of l-epinephrine resulted in a dose-related increase in plasma ACTHi and B. Maximal levels were similar to those observed during ether stress. The pituitary-adrenal system appeared more sensitive than the cardiovascular system to epinephrine, since the ED50 values of epinephrine for its effects on ACTHi and heart rate were 165 and 840 ng/kg . min, respectively. The effect of epinephrine on pituitary-adrenal activity could be mimicked by the beta-adrenergic agonist l-isoproterenol and could be blocked by the beta-adrenergic antagonist l-propranolol, whereas d-propranolol was ineffective. The response of the pituitary-adrenal system to epinephrine was not caused by effects on peripheral parameters such as the distribution or clearance of ACTH or B but was mediated by an increase in ACTH release. The pituitary-adrenal response to epinephrine and isoproterenol was not related to changes in heart rate, blood pressure, or vasopressin secretion. Infusion of epinephrine at a dose that induced a maximal increase in plasma ACTHi and B (1000 ng/kg . min) resulted in a circulating epinephrine concentration of 11 pmol/ml, which is within the physiological range. From these data we conclude that 1) circulating epinephrine can stimulate pituitary-adrenocortical activity, 2) this action is mediated by a beta-adrenergic receptor mechanism, and 3) such a mechanism may be involved in the response of the pituitary-adrenal axis during certain forms of stress.

Anterior hypothalamic implantations of crystalline atropine markedly inhibit the adrenocortical responses evoked by surgical stress, ether anesthesia, or intravenolus injection of arginine vasopressin. Similar implants in nearby regions of the brain or sham implantations in the same region were ineffective. The data suggest that the hypothalamic control of pituitary corticotropin may have a cholinergic component.

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