Aldosterone and Ang II complementary stimulate ENaC activity during systemic salt restriction

Abstract

Dietary salt intake controls ENaC activity via renin‐angiotensin‐aldosterone system (RAAS) and aldosterone is considered to be a key modulator. However, experimental evidence suggests possible involvement of other RAAS components (such as Ang II) in ENaC regulation additively to aldosterone. Using patch‐clamp electrophysiology in split‐opened distal nephrons, we demonstrate that Ang II, acting via AT1 receptors, acutely stimulates ENaC open probability (Po) and this effect is preserved, when aldosterone levels are clamped high with DOCA. Application of aldosterone does not reproduce the acute stimulatory action of Ang II. Dietary salt restriction (<0.01% Na+ for 7 days) increases both functional ENaC expression (fN) and ENaC Po. Systemic inhibition of mineralocorticoid receptors with spironolactone (7 days) attenuates ENaC activity by decreasing fN, but not Po. Simultaneous treatment with spironolactone and losartan (AT1 receptor antagonist) virtually abolished elevations of ENaC fN and Po by salt restriction. We conclude that Ang II and aldosterone complementary contribute to proper ENaC activation in response to dietary salt restriction, acting primarily on Po and fN, respectively.