There is evidence suggesting that the control of aldosterone secretion is relatively independent of the pituitary gland. This is based on morphological studies in the rat (1), on indirect assessments of adrenal secretion during metabolic studies in man (2), and on direct estimations of adrenal hormone secretion in the rat (3, 4) and dog (5-7). The morphological studies of Deane and Masson (8), which indicate that renin may stimulate the adrenal cortex in the rat, the results of Genest and his colleagues (9), which suggest that arterial hypertension may be associated with an increased excretion of aldosterone in man, and the demonstration by Genest ( 10, 11 ) and Laragh (12) and their colleagues that angiotensin II stimulates excretion (10, 11) and secretion (12, 13) of aldosterone suggest that the kidney may have some influence on the rate of secretion of adrenal hormones. Recently, Pronove, MacCardle, and Bartter (14) described a dwarfed, normotensive child who was suffering from the effects of excessive production of aldosterone. This was associated with a remarkable hypertrophy and hyperplasia of the juxtaglomerular apparatus in the kidney. The syndrome has been found subsequently in two other patients with hyperaldosteronism (15, 16). The observations suggested that the kidney itself was in some way responsible for the overproduction of aldosterone. The present experiments, performed in the dog, were designed to test the hypothesis that the normal kidney contains material capable of stimulating the adrenal cortex. This was found to be so (17,18), in agreement with results simultaneously obtained by Mulrow, Ganong, Cera, and Kuljian (19) and by Davis and associates (20,21). Accordingly, further studies were designed to see whether the pattern of response of the three important adrenocortical steroid hormones (aldosterone, cortisol, and corticosterone) was such as to suggest that this renal stimulus is involved in the mediation of aldosterone secretion physiologically.
MATERIAL AND METHODSThe effects of hypophysectomy in unanesthetized dogs were tested in eight dogs fed a diet containing 9 mEq of sodium and 186 mEq of potassium for 13 to 21 days. On day 1, the lumbo-adrenal vein was cannulated, and the right kidney was removed under Nembutal or ether anesthesia. On day 2, two adrenal blood samples were collected without anesthesia with the animal lying quietly. The pituitary was then removed under Nembutal or halothane anesthesia. The next morning (about 18 hours after hypophysectomy), two adrenal blood samples were again collected without anesthesia, with the animal lying quietly. All animals received 100 mg cortisone acetate intramuscularly on the day of hypophysectomy.Infusion studies. Male mongrel dogs weighing between 16.4 and 26.5 kg were anesthetized with Nembutal, and the pituitary was removed by a buccal approach 2 to 4 hours before the beginning of each experiment, except as otherwise indicated. Both kidneys were removed between double ligatures on the renal pedicles, and a cannula was inserted in...