Hypertension. 2003;41:1143-1150
Published online before print April 7, 2003, doi: 10.1161/01.HYP.0000066129.12106.E2
Published online before print April 7, 2003, doi: 10.1161/01.HYP.0000066129.12106.E2
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(Hypertension. 2003;41:1143.)
© 2003 American Heart Association, Inc.
Scientific Contributions |
Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II
From the Laboratory of Kidney and Electrolyte Metabolism, NHLBI, National Institutes of Health (K.T.B., S.M., S.T., J.N., H.L.B., S.A., R.A.F., M.A.K.), Bethesda, Md; and Department of Biological Sciences, George Washington University (K.T.B., R.K.P.), Washington, DC.
Correspondence to Mark A. Knepper, MD PhD, National Institutes of Health, 10 Center Dr MSC 1603, Bethesda, MD 20892-1603. E-mail knep{at}helix.nih.gov
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 (AT1 receptor) antagonist, candesartan, (1 mg/kg of body weight per day SC for 2 days) markedly decreased the abundance of the 
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 ENaC protein abundance in rat kidney cortex. The decrease in ENaC protein abundance in response to AT1 receptor blockade was associated with a fall in ENaC mRNA abundance (real-time RT-PCR), consistent with transcriptionally mediated regulation. The effect of AT1 receptor blockade on ENaC expression was not blocked by spironolactone, suggesting a direct role of the AT1 receptor in regulation of ENaC gene expression. Candesartan administration was also found to increase the abundances of the ß and 
subunits. The increase in ß and ENaC 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 ß and ENaC 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.
Key Words: receptors, angiotensin II • angiotensin antagonist • sodium channels • aldosterone
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