EFFECT OF STEROIDS ON WATER DIURESIS AND VASOPRESSIN SENSITIVITY *

The ability of glucocorticoids to reverse the abnormal diuretic response to water in adrenal insufficiency (1-5) and to increase water diuresis in normal subjects (6, 7) is well known. Although glucocorticoids appear to be specific in this regard, the possibility that other steroids may have a pharmacologic effect on water diuresis in normal man has not been investigated systematically. The present study was therefore undertaken to compare the effects of large doses of cortisol, progesterone, estrogen and aldosterone on the maximal rate of free water clearance during water diuresis in normal man. The effects of low sodium diet and an aldosterone antagonist also were examined. It was found that only cortisol appeare

STUDIES ON THE RENAL CONCENTRATING MECHANISM. V. EFFECT OF DIURETIC AGENTS *

Evidence for the site of action of diuretic drugs in man can be derived from observations of their effect on different tubular functions. Previous studies have shown that mercurial diuretic agents have little influence on water diuresis or antidiuresis (1-5) and hydrogen ion secretion (6, 7). These observations have been taken to indicate that the predominant action of these mercurial agents is to decrease sodium reabsorption in the proximal tubule. A proximal site of action has also been suggested by stop flow analysis of tubular function during combined mercurial and mannitol diuresis (8-10). The similarity between osmotic and mercurial diuresis has been emphasized (5, 8, 11, 12) but these states have not been compared directly in man. The present study concerns the effects of diuretic drugs on renal concentrating ability in healthy hydropenic young men. The urine was found to be less concentrated during mercurial diuresis when compared with mannitol diuresis at similar urine flows. This difference was greatest when mercurial action was potentiated by the prior administration of ammonium chloride. The data provide evidence that mercurial diuretic agents can act on those portions of the nephron involved in the renal concentrating process, presumably beyond the proximal tubule. Acetazolamide and chlorothiazide, drugs which probably act both distally and proximally (8, 13-15) were also studied. The former was found to decrease concentrating ability, while the latter had little effect. METHODS Experimental procedure. The subjects were 6 paid volunteer medical students, ages 25 to 28 years, wh