The Effect of Acth, Renin, Angiotensin Ii, and Various Precursors on Biosynthesis of Aldosterone by Adrenal Slices

Abstract

Angiotensin II has been shown to increase the excretion (1) and secretion (2) of aldosterone by normal human subjects, and the secretion of aldosterone by hypophysectomized, nephrectomized dogs (3)(4)(5). In the latter preparation (3), renin, which leads to the liberation of angiotensin in the circulation (6), has been shown to stimulate aldosterone secretion. The present studies were done to determine whether angiotensin and renin can act directly on the adrenal cortex. The slices were minced with scissors and weighed. Specimens weighing about 500 mg were placed in 5 ml of Krebs-Ringer bicarbonate medium containing glucose in a concentration of 200 mg per 100 ml. At least 4 vessels were incubated and analyzed separately for each portion of each experiment. Thus, there were at least 4 control vessels and at least 4 with each precursor or stimulating agent studied in each experiment. The tissues were kept chilled until incubation, which was started between 3 and 5 hours after the death of the cattle. Tissues were preincubated for 1 hour at 37°C under 5 per cent CO2-95 per cent 02 on the Dubnoff metabolic shaker. The preincubation medium was removed, and 5 ml of fresh medium was used to transfer the slices to vessels to which the appropriate precursor had been added with or without ACTH, renin, or angiotensin II. Incubation was for 2 hours.The control values for synthesis of aldosterone by the adrenals in vitro showed wide variations from experiment to experiment. The higher the control value, the less was the effect of any given stimulus. Thus, when production of aldosterone by the control beef slices was greater than 2 gsg per g of tissue per hour, experimental procedures produced little or no increase of synthesis. Therefore, only preparations with control values below 2 ,lg per g per hour are included. Factors which may have affected the control level of aldosterone production were water and salt deprivation. Control values were above 4 ,ug per g per hour only during the winter months when the ground was frozen and the cattle had no access to water for at least 24 to 48 hours before slaughter and limited access to water and salt for a longer period. A stimulatory effect of water deprivation on synthesis of aldosterone in vivo (7) and of salt depletion on synthesis in vitro (8) has been observed. Other factors may have led to this seasonal variation, a problem noted by others studying corticosteroid synthesis in vitro (9).The capacity of the tissue to respond to any given stimulus was found to decrease with the passage of time, so this was kept relatively constant in all experiments.Rat adrenal sections. The technique of Saffran and Schally (10) was closely followed. A quarter of one adrenal gland from each of eight 150-to 200-g SpragueDawley male rats was included in each of four vessels 715

Reduced Vascular Response to Angiotensin Ii in Secondary Hyperaldosteronism*

“…The renin content of kidney tissue correlates well with the thickness of the zona glomerulosa of the adrenal cortex and with the measured aldosterone production rate (3,4). Angiotensin has been shown to stimulate aldosterone production both in man (5,6) and in intact animals (4,7), and it is a powerful stimulus to the biosynthesis of aldosterone in vitro (4,8). Although its role under normal physiological conditions is not clear (7), the renin-angiotensin system has been implicated in the maintenance of certain states of experimentally produced hyperaldosteronism (9), and angiotensin may be an aldosterone-stimulating hormone (ASH).…”

Studies of the mechanism through which sodium depletion increases aldosterone biosynthesis in man.

“…It has been suggested that angiotensin might be the mediator of the natropenic stimulus to aldosterone secretion (11,12,14), and it has been observed that angiotensin acts early in the aldosterone biosynthetic pathway (5). In designing the present study we preferred to make no assumptions as to whether angiotensin is the mediator of the natropenic stimulus to aldosterone secretion.…”

Specific action of the lipoxygenase pathway in mediating angiotensin II-induced aldosterone synthesis in isolated adrenal glomerulosa cells.

“…Angiotensin II (AII),' potassium (K+), and ACTH are the major stimulators of aldosterone synthesis in vitro and in man (1)(2)(3) All three agonists activate the calcium messenger system, however, only All induces the hydrolysis of phosphoinositides and releases intracellular calcium (4)(5)(6). After binding to its receptor, All activates phospholipase C, which induces the formation of diacylglycerol and the release of arachidonic acid (AA) (7).…”