Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II
- 1 May 2003
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 41 (5), 1143-1150
- https://doi.org/10.1161/01.hyp.0000066129.12106.e2
Abstract
We carried out semiquantitative immunoblotting of kidney to identify apical sodium transporter proteins whose abundances are regulated by angiotensin II. In NaCl-restricted rats (0.5 mEq Na/200 g BW/d), the type 1 angiotensin II receptor (AT 1 receptor) antagonist, candesartan, (1 mg/kg of body weight per day SC for 2 days) markedly decreased the abundance of the α subunit of the epithelial sodium channel (ENaC). This subunit has been shown to be rate-limiting for assembly of mature ENaC complexes. In addition, systemic infusion of angiotensin II increased αENaC protein abundance in rat kidney cortex. The decrease in αENaC protein abundance in response to AT 1 receptor blockade was associated with a fall in αENaC mRNA abundance (real-time RT-PCR), consistent with transcriptionally mediated regulation. The effect of AT 1 receptor blockade on αENaC expression was not blocked by spironolactone, suggesting a direct role of the AT 1 receptor in regulation of αENaC gene expression. Candesartan administration was also found to increase the abundances of the β and γ subunits. The increase in β and γENaC protein abundance was not associated with a significant increase in the renal abundances of the corresponding mRNAs, suggesting a posttranscriptional mechanism. Immunocytochemistry confirmed the increase in β and γENaC protein abundance and demonstrated candesartan-induced ENaC internalization in collecting duct cells. The results support the view that the angiotensin II receptor regulates ENaC abundance, consistent with a role for angiotensin II in regulation of collecting duct function.This publication has 29 references indexed in Scilit:
- Time course of renal Na-K-ATPase, NHE3, NKCC2, NCC, and ENaC abundance changes with dietary NaCl restrictionAmerican Journal of Physiology-Renal Physiology, 2002
- Effects of Aldosterone on Biosynthesis, Traffic, and Functional Expression of Epithelial Sodium Channels in A6 CellsThe Journal of general physiology, 2002
- Non-coordinate Regulation of Endogenous Epithelial Sodium Channel (ENaC) Subunit Expression at the Apical Membrane of A6 Cells in Response to Various Transporting ConditionsOnline Journal of Public Health Informatics, 2000
- Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assaysJournal of Molecular Endocrinology, 2000
- Pleiotropic action of aldosterone in epithelia mediated by transcription and post-transcription mechanismsKidney International, 2000
- Aldosterone-mediated regulation of ENaC α, β, and γ subunit proteins in rat kidneyJCI Insight, 1999
- Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo.JCI Insight, 1996
- PCR localization of angiotensin II receptor and angiotensinogen mRNAs in rat kidneyKidney International, 1993
- An in vivo study of voltage-dependent renal tubular acidosis induced by amilorideKidney International, 1989
- Calcium and cyclic adenosine monophosphate as second messengers for vasopressin in the rat inner medullary collecting duct.JCI Insight, 1988