The Aldosterone Paradox: differential regulation of the sodium chloride cotransporter

Abstract

Maintaining total body Na+ and K+ balance is essential to the survival of most species. Hypovolemia (Na+ deficit) and hyperkalemia (K+ surplus) elicit different constellations of responses to maintain homeostasis. During hypovolemia, the extracellular fluid volume needs to be maintained to guarantee blood pressure and organ perfusion. Conversely, during hyperkalemia, K+ secretion is stimulated to avoid cardiac and neuromuscular complications. Both these physiological conditions are regulated by the mineralocorticoid hormone aldosterone which is part of the renin-angiotensin-aldosterone system (RAAS). The observation that a single hormone, aldosterone, has different effects on renal Na+ and K+ transport, depending on the physiological situation, has been termed the “aldosterone paradox”. How the kidney “knows” when to retain Na+ or secrete K+ during these two high aldosterone states is unknown. To understand the aldosterone paradox, it is important to briefly review the regulation of Na+ and K+ transport in the kidney.