Medline ® Abstracts for References 3-5

Aldosterone is part of a complex system that regulates plasma potassium concentration by affecting the renal excretion of the ion as well as its distribution within the body. Because there are other components of the system, it has been difficult to determine the physiological significance of aldosterone in potassium regulation by attempting to study the hormone's effects in isolation. In this presentation a quantitative analysis of the potassium control system is used to provide information concerning the physiological role of aldosterone in potassium regulation under normal and pathological conditions, as well as during pharmacological interventions.

The mechanisms responsible for renal potassium (K) conservation during dietary potassium deficiency are poorly understood. This study was undertaken to investigate the time course of potassium conservation as well as the roles of distal sodium (Na) delivery, the distal delivery or sodium plus a nonpermeable anion, mineralocorticoid hormone, renal tissue potassium content, and Na-K-ATPase activity in renal potassium conservation. After 72 hours of a low-potassium diet, basal potassium excretion was negligible. After 24 hours, and even more so after 72 hours of potassium restriction, the kaliuretic response to increasing distal delivery of sodium or sodium plus a nonpermeable anion was impaired. After 24 hours of a low-potassium diet, plasma aldosterone levels fell from 180 +/- 25 to 32 +/- 9 pg/ml (P less than 0.001). Mineralocorticoid hormone given in the first 24 hours of a low-potassium diet resulted in a greater potassium loss (1564 +/- 125 muEq) than it did in controls on the same diet not receiving mineralocorticoid hormone (1032 +/- 83 muEq, P less than 0.005). In contrast, after 72 hours of diet, large doses of mineralocorticoid hormone failed to cause a kaliuresis in either anesthetized or conscious rats. After both 24 and 72 hours, outer medullary Na-K-ATPase was increased. At 72 hours, cortical, medullary, and papillary tissue potassium concentrations were significantly depressed. Acute administration of potassium repleted tissue potassium levels and restored basal and saline-stimulated potassium excretion to normal. Although potassium excretion was markedly depressed after 24 hours of the low-potassium diet, 42K microinjection studies of the distal nephron did not suggest any increase in potassium reabsorption. Following 72 hours of diet, potassium reabsorption increased significantly from 26 +/- 2% to 41 +/- 2% (P less than 0.001). We conclude that renal potassium conservation is at first primarily related to a decrease in potassium secretion, which is most likely mediated by falling levels of mineralocorticoid hormone. After 72 hours of the potassium-deficient diet, however, potassium conservation becomes independent of mineralocorticoid hormone, distal delivery of sodium, and Na-K-ATPase. The decreased tissue potassium content appears to be the primary mediator of both the increase in potassium reabsorption by the distal nephron and of renal potassium conservation at this time.

This review provides an overview of the molecular mechanisms of K transport in the mammalian connecting tubule (CNT) and cortical collecting duct (CCD), both nephron segments responsible for the regulation of renal K secretion. Aldosterone and dietary K intake are two of the most important factors regulating K secretion in the CNT and CCD. Recently, angiotensin II (AngII) has also been shown to play a role in the regulation of K secretion. In addition, genetic and molecular biological approaches have further identified new mechanisms by which aldosterone and dietary K intake regulate K transport. Thus, the interaction between serum-glucocorticoid-induced kinase 1 (SGK1) and with-no-lysine kinase 4 (WNK4) plays a significant role in mediating the effect of aldosterone on ROMK (Kir1.1), an important apical K channel modulating K secretion. Recent evidence suggests that WNK1, mitogen-activated protein kinases such as P38, ERK, and Src family protein tyrosine kinase are involved in mediating the effect of low K intake on apical K secretory channels.