Document Detail


Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.
MedLine Citation:
PMID:  20686170     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.
Authors:
Crystal West; Zheng Zhang; Geoffrey Ecker; Shyama M E Masilamani
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-04
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  299     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-03     Completed Date:  2010-12-01     Revised Date:  2011-11-01    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1326-32     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine/Division of Nephrology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0160, USA.
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MeSH Terms
Descriptor/Qualifier:
Aldosterone Antagonists / pharmacology
Amiloride / analogs & derivatives,  pharmacology
Animals
Epithelial Sodium Channel / antagonists & inhibitors,  metabolism*
Female
Immunoblotting
Kidney / drug effects,  metabolism*
Mineralocorticoids / metabolism
Natriuresis
Plasma Volume
Pregnancy
Proteomics
Rats
Rats, Sprague-Dawley
Sodium / metabolism*
Sodium Channel Blockers / pharmacology
Spironolactone / analogs & derivatives,  pharmacology
Up-Regulation
Grant Support
ID/Acronym/Agency:
K22HL66994/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Aldosterone Antagonists; 0/Epithelial Sodium Channel; 0/Mineralocorticoids; 0/Scnn1a protein, rat; 0/Sodium Channel Blockers; 0/eplerenone; 2609-46-3/Amiloride; 2898-76-2/benzamil; 52-01-7/Spironolactone; 7440-23-5/Sodium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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