Davis, James O.

Secretion of aldosterone and corticosterone was studied in conscious dogs by means of a chronic indwelling catheter to obtain adrenal vein blood. In most conscious normal dogs, steroid secretion was lower than in anesthetized normal animals following acute adrenolumber vein cannulation. However, in dogs not well trained or excitable, secretion of aldosterone and corticosterone was strikingly elevated above the basal output. This finding probably reflects an increased plasma level of ACTH. In dogs with thoracic caval constriction, aldosterone output was markedly increased above normal whereas corticosterone and Porter Silber chromogen secretion was frequently very low, a finding which suggests a normal plasma level of ACTH. Hypophysectomy of dogs with caval constriction resulted in a greater, more abrupt fall in corticosterone than in aldosterone secretion. In two of these dogs, aldosterone secretion fell to normal or below within 2 days, whereas in the other two dogs, aldosterone output, although reduced, remained above normal for several days. Porter Silber chromogens showed changes similar to those observed for corticosterone. It is concluded that the anterior pituitary provided important support for increased aldosterone production but was unessential for hypersecretion of aldosterone.

Effects of hypophysectomy on aldosterone and sodium excretion were studied in a group of seven dogs with ascites secondary to thoracic inferior vena cava constriction. In another group of three dogs, the pituitary was removed first and after 6–8 weeks the thoracic inferior vena cava was constricted. Following hypophysectomy of the seven dogs with the initial ascites, aldosterone became undetectable in urine and sodium excretion increased concurrently; adrenocorticotrophic hormone (ACTH) failed to prevent these effects. However, additional constriction of the vena cava with a consequent further elevation in venous pressure was followed by a return of nearly complete sodium retention. In two of the dogs in which hypophysectomy was performed first and the thoracic inferior vena cava constricted later, there resulted increased aldosterone output, marked sodium retention and ascites. In these dogs the adrenal cortex was markedly atrophic but the atrophy was limited to the two inner layers. The data suggest that in pathological states accompanied by edema and ascites the increased excretion and presumably increased secretion of aldosterone are not solely dependent upon pituitary hormonal function.

Effects of hypothalamic lesions were studied in 10 dogs with chronic ascites produced by constriction of the thoracic inferior vena cava. During the first three postoperative days, the high rate of urinary aldosterone excretion and the marked Na retention characteristic of dogs with chronic experimental ascites were unaltered in all 10 animals. Every area of the hypothalamus was destroyed bilaterally in at least one animal. Seven of the 10 dogs survived the subacute 3-day period; two dogs died after 6 days but five animals lived for 2 weeks or longer. In these seven animals, aldosterone excretion in urine remained elevated above normal although in three animals a progressive decline occurred; sodium excretion remained low in all seven dogs surviving the subacute period. In the three animals in which aldosterone output declined, there was bilateral injury of the median eminence and adrenal atrophy. The data show that chronic hypothalamic lesions were without effect unless the median eminence was injured.

Acute effects of hypophysectomy and of diencephalic lesions on aldosterone and corticosterone secretion were studied in 10 dogs with chronic experimental ascites. During preliminary observations, diencephalic lesions were made by the oral approach but the pituitary gland was damaged; in two dogs aldosterone and corticosterone secretion fell markedly. In the third animal, ACTH was given following the lesion; aldosterone failed to fall while corticosterone declined slightly. In the definitive study (7 dogs), hypophysectomy was performed before the diencephalic lesion was made. Following hypophysectomy, a 76–97% decrease in aldosterone secretion occurred within 2 hours. The effects of diencephalic lesions were variable; aldosterone output was unchanged, increased, decreased and increased during the 1st hour but declined thereafter. Corticosterone secretion fell 81–99% after hypophysectomy. These acute observations show a striking dependence of aldosterone and corticosterone secretion upon intact pituitary function. The evidence on the relation of the diencephalon to aldosterone secretion was inconclusive but an intact middle and posterior hypothalamus was not essential for normal or elevated rates of aldosterone secretion.