Evidence That a Humoral Agent Stimulates the Adrenal Cortex to Secrete Aldosterone in Experimental Secondary Hyperaldosteronism *

Abstract

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...

The Effect of Hemorrhage Upon Aldosterone Secretion in Normal and Hypophysectomized Dogs*

“…A great deal of evidence indicates that this mechanism is humoral (15)(16)(17)(18). The response within 15 minutes suggests that some component of intravascular volume, pressure or flow is the stimulus.…”

THE EFFECTS OF CHRONIC HEPATIC VENOUS CONGESTION ON THE METABOLISM OF d,l-ALDOSTERONE AND d-ALDOSTERONE*

“…Plasma, bile, and ascitic fluid were analyzed for aldosterone by the following procedure, which involved slight modifications of the double isotope derivative assay (7,8).…”

The Effect of Bilateral Nephrectomy and Midcollicular Decerebration with Pinealectomy and Hypophysectomy on the Corticosteroid Secretion of Sodium-deficient Sheep *

“…Lack of radiochemical purification could give too high a result. With the double isotope derivative method (5,8) where the marker is added only after extraction and acetylation, there is the additional possibility of unknown handling losses and incomplete esterification, which despite adequate radiochemical purification could lead to a low estimate. Data in relation to the error of the double isotope dilution derivative method and the method blank have been published (2).…”

“…Crosscirculation studies of Denton, Goding, and Wright (1) and Yankopoulos, Davis, Kliman, and Peterson (5) indicate that the stimulus to the adrenal is humoral. Three local humoral circumstances, ACTH infusion (2,(6)(7)(8), angiotensin II infusion (2,6,(9)(10)(11)(12), and low sodium and high potassium concentration of plasma (1,2,6,13), are known to cause an increase in aldosterone secretion, and the levels required for the reaction are not beyond those that are known or might be presumed to occur naturally.…”