Angiotensin II-Type-1a Receptor and Renal K + Wasting during Overnight Low-Na + Intake.

Abstract

Angiotensin II–type-1a-receptor in the distal convoluted tubule (DCT) plays a role in regulating sodium transport in the DCT. Angiotensin II–type-1a-receptor in the DCT plays a role in maintaining potassium homeostasis during sodium restriction. Chronic angiotensin II perfusion stimulates Kir4.1/Kir5.1 of the distal convoluted tubule (DCT) <i>via</i> angiotensin II–type-1a-receptor (AT1aR), and low‐sodium intake also stimulates Kir4.1/Kir5.1. However, the role of AT1aR in mediating the effect of low salt on Kir4.1/Kir5.1 is not explored. We used the patch-clamp technique to examine Kir4.1/Kir5.1 activity of the DCT, employed immunoblotting to examine Na-Cl cotransporter (NCC) expression/activity, and used the <i>in vivo</i> perfusion technique to measure renal Na⁺ and renal K⁺ excretion in control, kidney tubule–specific–AT1aR-knockout mice (Ks-AT1aR-KO) and DCT-specific–AT1aR-knockout mice (DCT-AT1aR-KO). Angiotensin II acutely stimulated the 40-pS-K⁺ channel (Kir4.1/Kir5.1-heterotetramer) and increased whole-cell Kir4.1/Kir5.1-mediated K⁺ currents and the negativity of DCT membrane potential only in late DCT2 but not in early DCT. Acute angiotensin II increased thiazide-induced renal Na⁺ excretion (E_Na). The effect of angiotensin II on Kir4.1/Kir5.1 and hydrochlorothiazide-induced E_Na was absent in Ks-AT1aR-KO mice. Overnight low-salt intake stimulated the expression of <i>Agtr1a</i> mRNA in DCT, increased whole-cell Kir4.1/Kir5.1-mediated K⁺ currents in late DCT, hyperpolarized late DCT membrane, augmented the expression of phosphor-Na-Cl-cotransporter, and enhanced thiazide-induced renal-E_Na in the control mice. However, the effect of overnight low-salt intake on Kir4.1/Kir5.1 activity, DCT membrane potential, and NCC activity/expression was abolished in DCT-AT1aR-KO or Ks-AT1aR-KO mice. Overnight low-salt intake had no effect on baseline renal K⁺ excretion (E_K) and plasma K⁺ concentrations in the control mice, but it increased baseline renal-E_K and decreased plasma K⁺ concentrations in DCT-AT1aR-KO or in Ks-AT1aR-KO mice. Acute angiotensin II or overnight low-salt intake stimulated Kir4.1/Kir5.1 in late DCT, and AT1aR was responsible for acute angiotensin II or overnight low-salt intake–induced stimulation of Kir4.1/Kir5.1 and NCC. AT1aR of the DCT plays a role in maintaining adequate baseline renal-E_K and plasma K⁺ concentrations during overnight low-salt intake.