The mechanisms which effect alterations in the secretion of aldosterone by the adrenal cortex may be nervous, humoral or both. The present study was undertaken to examine the possibility that a humoral agent stimulates the adrenal cortex to secrete aldosterone in dogs with experimental secondary hyperaldosteronism produced by constriction of the thoracic inferior vena cava. These animals secrete large amounts of aldosterone (1) and show almost complete retention of Na (2). To test the hypothesis of a humoral mechanism, the effect on aldosterone secretion was studied in normal recipient animals or in the isolated adrenals of normal dogs during cross-circulation of blood from dogs with constriction of the thoracic inferior vena cava. Corticosterone secretion was also measured to evaluate the possible role of adrenocorticotropic hormone (ACTH) in the aldosterone regulatory system. METHODSThe basic plan of the experiments consisted of crosscirculation of blood from a donor into a recipient animal or into the isolated adrenal glands of a recipient animal. Secondary hyperaldosteronism was produced in the donor animals by either acute or chronic constriction of the thoracic inferior vena cava. Acute caval constriction was performed on normal dogs. In the chronic donor dogs, ascites had been present for one to three weeks, and Na excretion on the day before the experiment was less than 4 mEq. per day; Na and K intakes were 60 and 18 mEq. per day, respectively. Also, aldosterone secretion from the right adrenal gland was measured in a group of eight dogs with chronic thoracic inferior vena cava constriction to determine the magnitude and consistency of hypersecretion. All animals were mongrel dogs which weighed 15 to 20 Kg. Nembutal® anesthesia was used.Each dog received 15,000 I.U. of heparin before collection of adrenal vein blood and before cross-circulation. * A preliminary report was given at the Laurentian Hormone Conference, September, 1958. After control determinations in both animals, the thoracic inferior vena cava was constricted in one of the dogs which became the donor. In the two other experiments of this group, dogs with chronic thoracic caval constriction were the donor animals. Under these circumstances, control observations were made in both the chronic donor and the normal recipient before crosscirculation was established.In the second group of experiments (15 pairs of dogs), blood was circulated from a donor animal with chronic thoracic caval constriction and ascites or from a normal dog into the isolated adrenals of a normal recipient animal (Figure 1). Cross-circulation of blood from normal dogs provided a control on the effect of cross-circulation per se. The recipient's adrenals were isolated in situ with segments of aorta and inferior vena cava by the procedure of Hilton and co-workers (3). Care was taken to include in the arterial circulation to the lower pole of the right adrenal gland a small artery arising from the aorta. Polyethylene tubing was used for all connections. During the control an...

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Previous reports (1-9) have delegated a secondary role to anterior pituitary hormones in the control of aldosterone secretion.' Although hypophysectomy resulted in decreased aldosterone secretion (3) or reduced urinary aldosterone output (2), hyperaldosteronuria, marked sodium (Na) retention and ascites occurred in the absence of the adenohypophysis in dogs with thoracic inferior vena cava constriction (2). Also, in patients with hypopituitarism, Luetscher and Axelrad (6) and Hernando and associates (7) found that urinary aldosterone output was within normal limits in some patients on an unselected diet or a normal salt intake, and Liddle, Duncan 'and Bartter (8) reported hyperaldosteronuria in one patient with hypopituitarism on a low Na diet.However, no conclusive evidence of hypersecretion 1 of aldosterone in the absence of anterior pituitary hormones has been reported. The critical pertinent data on the rate of aldosterone secretion during stimulation which produces hypersecretion in normal animals have not been reported for hypophysectomized dogs or patients. It is important that studies in man be conducted on hypophysectomized patients since patients with so-called panhypopituitarism may not have loss of all anterior pituitary function. Furthermore, our knowledge is incomplete on the importance of specific anterior pituitary hormones. Several studies (3,7,(8)(9)(10) have demonstrated an increase in aldosterone secretion or urinary aldo-* This investigation was aided in part by Grant A-1944 from the National Institutes of Health, Bethesda, Md.1 The phrases "aldosterone secretion" or "hypersecretion of aldosterone" have been used to refer to actual measurements of the rate of secretion by the adrenal gland into the effluent plasma and are to be distinguished from urinary aldosterone excretion. sterone excretion following administration of various corticotropin preparations, but the data are inadequate to establish the role of ACTH in secondary hyperaldosteronism.2The question of the role of the anterior pituitary in the control of aldosterone secretion was reopened by the finding of a 76 to 97 per cent fall in adrenal vein aldosterone output following hypophysectomy of dogs with experimental secondary hyperaldosteronism ( 11). In the present report, data are presented on the efficacy of ACTH 3 in preventing this fall in aldosterone secretion which follows hypophysectomy. Large doses of cortisone have been administered to inhibit ACTH secretion in dogs with hyperaldosteronism secondary to caval constriction; the resultant effects on aldosterone and corticosterone production were observed. Subsequently, the effects of hypophysectomy and ACTH were studied in these animals. Also, the effects of synthetic a-melanophore-stimulating hormone (MSH) and of highly purified preparations of natural a-and ,B-MSH have been studied. Attempts have been made to stimulate hypersecretion of aldosterone in simple hypophysectomized dogs by 1) a low Na diet and 2) acute constriction of the thoracic inferior vena cava.2 In this pap...

Aldosterone secretion (1) and aldosterone excretion in urine (2) are markedly elevated in dogs with chronic right heart failure and in dogs with chronic ascites secondary to thoracic caval constriction. It was suggested that the adrenal cortex is stimulated to secrete aldosterone by factors resulting from a high venous pressure and the consequent loss of fluid and electrolytes from the blood stream. The precise nature of these factors remains to be defined.The purpose of the present study was threefold: 1) to determine the effects of acute caval constriction on aldosterone secretion in an attempt to develop an acute experimental preparation for evaluation of factors influencing aldosterone secretion; 2) to evaluate the effect of changes in vascular volume on aldosterone output; and 3) to apply a radioisotope derivative technique developed by two of us (B. K. and R. E. P.) for the determination of aldosterone and corticosterone in 2 ml. samples of adrenal vein plasma. METHODS

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