Abstract
KEY POINTS: 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. BACKGROUND: Chronic angiotensin II perfusion stimulates Kir4.1/Kir5.1 of the distal convoluted tubule (DCT) via 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. METHODS: 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 in vivo 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). RESULTS: 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 Agtr1a 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. CONCLUSIONS: 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.