The Nature of the Action of Intravenous Aldosterone: Evidence for a Role of the Hormone in Urinary Dilution*

Abstract

Aldosterone increases the renal retention of sodium chloride and promotes the excretion of potassium ions ( 1-11 ); but where and how the hormone acts in the renal tubule is poorly understood. The present study was designed to characterize further the mode and site of action of aldosterone in the nephron.Information can be obtained about the site of action of a compound by observing its effect on free water formation (12). According to a current concept of renal physiology (13), reabsorption of solute (sodium chloride) is isosmotic in the proximal tubule (14), whereas, in the more distal segments, reabsorption may or may not be isosmotic (15,16). During water diuresis (absence of antidiuretic hormone) the distal reabsorption of solute is selective, i.e., occurs without isosmotic amounts of water, leaving "solute-free" water behind for excretion (17). Thus, by determining the effect of a compound on solute excretion and on free water formation during maintained water diuresis, information may be obtained about its site of action (12). If aldosterone were to act to promote isosmotic reabsorption of sodium, the consequent reduction in solute excretion would be accompanied by a fall in urine flow and no change or fall in free water excretion. However, if aldosterone acts only at a more distal site, where reabsorption is selective, the reduced sodium excretion would be accompanied by no change in urine flow and hence, by a rise in free water excretion.In the present study it has been shown that aldosterone can promote abstraction of sodium chloride exclusive of water from the tubular urine. This action takes place in the tubule at a locus distal to that of isosmotic reabsorption. Also, this effect of the hormone on sodium chloride reabsorption appears to be dissociated from the effect on potassium excretion. EXPERIMENTALSeven studies were performed on 3 subj ects without evidence of renal or cardiovascular disease. Four of the experiments were done with subj ects maintained on a normal NaCl intake (4 to 6 g NaCl per day for 7 days), two with the subj ects on a higher intake of salt for 7 days (8 to 20 g NaCl per day), and one after drastic salt deprivation (less than 250 mg per day for 6 days). In two subjects on normal salt intake, control studies of similar protocol but without administration of aldosterone were performed. All experiments were conducted in the fasting state at the same early morning hour with the subjects in a recumbent position.Water diuresis was induced by having the patient ingest about 1,500 ml of water by mouth during the hour before the experiment and was subsequently maintained by intravenous infusion of 5 per cent dextrose and water at a constant rate, at least 2 ml per minute greater than urinary output. Adequate control periods were obtained until a steady state of maximum urine flow was demonstrated, so that any subsequent change in free water clearance could not be attributed to an increasing water diuresis.When a steady state of maximum water diuresis had been achieved, 1 mg of d,l-ald...

The antinatriuretic action of gamma‐L‐glutamyl‐5‐hydroxy‐L‐tryptophan is dependent on its decarboxylation to 5‐hydroxytryptamine in normal man.

“…The prodrug also increases aldosterone production as previously reported but the time course of the changes in sodium excretion and the lack of effect on urinary potassium excretion suggest that the antinatriuresis occurs independently of the known actions of aldosterone [6,9]. Both the enzymes required for 5-HT synthesis from glu-5-HTP, yGT and LAAD, are highly concentrated in the proximal tubular cells of the kidney [3,10] and the high urinary levels of 5-HT would indicate that 5-HT is probably formed in the renal tubules and then excreted.…”

The effect of uncomplicated potassium depletion on urine acidification

“…Therefore some mechanism other than a change in potassium concentration in some body compartment appears to be necessary to explain fully the decrease in K+/(k++H+) ratio. A possible explanation would be that aldosterone effects the renal tubule by selectively altering only sodiumpotassium exchange; however, most evidence suggests that it always affects hydrogen ion exchange concomitantly as well (36)(37)(38)(39). It is tempting to speculate that this unexplained decrease in potassium excretion might be the result of an increase in renal ammonia production accompanying potassium depletion.…”

Influence of Expansion of Extracellular Volume on Tubular Reabsorption of Sodium Independent of Changes in Glomerular Filtration Rate and Aldosterone Activity *

“…Therefore, if expansion of ECF volume selectively inhibits sodium reabsorption in the distal nephron, the increased sodium excretion should be associated with a proportionate drop in CH90 and no increase in urine volume (19). If, on the other hand, there is either selective depression of sodium reabsorption in the proximal nephron or hyperperfusion of nephrons, the delivery of isosmotic fluid to the distal nephron should increase, and the ensuing natriuresis should be accompanied by both increased urine flow and increased CH>O, as well as a decrease in the calculated fraction of filtrate reabsorbed in the proximal nephron.…”