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

Author:

Duan Xin-Peng12ORCID,Zheng Jun-Ya2,Xiao Yu23,Zhang Cheng-Biao12,Lin Dao-Hong2ORCID,Wang Wen-Hui2ORCID

Affiliation:

1. Department of Physiology, School of Basic Medical Science, Xuzhou Medical University, Xuzhou, China

2. Department of Pharmacology, New York Medical College, Valhalla, New York

3. Department of Physiology, Qiqihar Medical College, Heilongjiang, China

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 (ENa). The effect of angiotensin II on Kir4.1/Kir5.1 and hydrochlorothiazide-induced ENa 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-ENa 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 (EK) and plasma K+ concentrations in the control mice, but it increased baseline renal-EK 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-EK and plasma K+ concentrations during overnight low-salt intake.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

National Science Foundation of China

Publisher

Ovid Technologies (Wolters Kluwer Health)

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