Effects of Aldosterone and Cortisol on Henle's Loop in the Adrenalectomized Rat's Kidney

Abstract

It is generally accepted that urine is concentrated by the mammalian kidney through the operation of a countercurrent mechanism in the renal medulla and that active sodium transport out of the ascending limb of Henle's loop plays an important role in this mecha nism. In addition, it has been reported that in the adrenalectomized rat urine volume is decreased and the corticomedullary osmotic gradient lowered (1, 2).Experiments studying the effects of aldosterone on free water clearance (3) and the attainment of maximum urinary osmolality (4), have suggested that aldosterone may cause an increased rate of transport of sodium from the inside of the ascending limb of Henle's loop to the surrounding tissue. On the other hand, the action of glucocorticoids, particu larly their effects on the loop of Henle have not yet been precisely defined. Experiments dealing with free water reabsorption (T°H2O) indicated, that glucocorticoids may enhance sodium transport at the ascending limb (5, 6). Hierholzer's experiments (7) suggested that cortisol affects the water permeability of distal tubular segments. In the present experiments we have attempted, by microperfusion of Henle's loop in the kidneys of ad renalectomized rats, to clarify the mode of action of corticosteroids on these tubular seg ments. METHODSMale albino rats weighing 150-230g were adrenalectomized and given free access to 0.9% saline and a dry pellet diet. Intact rats were kept on tap water. The following groups of rats were studied (a) intact animals on controls, (b) adrenalectomized animals 18-24 hours, 4 days and 7-9 days after operation, (c) animals adrenalectomized 7-9 days previously and given 12.5 micrograms of d-aldosterone monoacetate (Aldocorten, Ciba) subcutaneously prior to anesthesia. A further dose of 3.1 micrograms was given intra venously when the kidney had been prepared for micropuncture, (d) animals adrenalecto mized 7-9 days previously and given a subcutaneous injection of 2.5 mg cortisol (alcohol free, Merck) for 2 days. In some animals of this group, 5 mg of cortisol was given daily for 3 days prior to micropuncture. (e) The final group of animals were given both a] dosterone and cortisol similarly to those of group c and d.

Mechanism of increased renin release in the adrenalectomized rat. Adrenal insufficiency and renin.

“…Other investigators have also reported that glucocorticoid replacement increases net sodium reabsorption in the loop of Henle of the adrenalectomized rat and corrects the water clearing defect in Addisonian patients and adrenalectomized dogs. 15 ' ' 6 In conclusion, we have previously suggested that inhibition of renin release by sodium chloride is related to increased absorptive chloride transport in the thick ascending limb of the loop Henle. Renin release is increased in the adrenalectomized rat and is not inhibited by infusion of sodium chloride.…”

Sodium- and potassium-activated ATPase. A possible target of aldosterone.

“…One group of investigators reported a correction of impaired sodium reabsorption at both tubular sites by aldosterone (15,23). This could not be confirmed by others (24,25).…”

Renal Pharmacology, with Special Emphasis on Aldosterone and Angiotensin

“…After administration of aldosterone or of cortisol, early distal tubular fluid, TF/P[Na +], and TF/P osm. tended to fall towards normal (53). This effect was more pronounced when aldosterone and cortisol were given simultaneously.…”