Document Detail


Regulation of endothelin-converting enzyme 1 in nephrotic syndrome in rats.
MedLine Citation:
PMID:  12972712     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Nephrotic syndrome is characterized by severe proteinuria and sodium and water retention. Although endothelin (ET) 1 can cause natriuresis or antinatriuresis, the role played by ET-1 in proteinuria and in sodium retention due to nephrotic syndrome remains unclear. METHODS: We investigated the role played by the ET-1 system in sodium and water retention and in proteinuria in puromycin aminonucleoside induced nephrotic syndrome in rats using microdissected nephron segments, competitive polymerase chain reaction, and Western blot. RESULTS: The expression of prepro ET-1, ET-converting enzyme 1 (ECE-1), and ET A receptor mRNAs, but not ET B receptor mRNA, in the glomeruli was increased in rats with nephrotic syndrome. The cGMP generation in the glomeruli induced by atrial natriuretic peptide and ET-1 was decreased, whereas the ET-3-induced cGMP generation was increased in rats with nephrotic syndrome. ECE-1 mRNA expression was increased not only in the glomeruli, but also in the thick ascending limbs and collecting ducts. The protein expression of ECE-1 was increased in the membrane fraction of the cortex and in the outer and the inner medulla of nephrotic rats. Blockade of ET A and B receptors by bosentan did not inhibit the occurrence of nephrotic syndrome. However, the administration of bosentan increased the urinary sodium excretion. CONCLUSION: These data suggest that an activated ET-1-ET A receptor pathway in glomeruli and/or an increased ECE-1 mRNA expression in distal segments may participate in sodium and water retention, but not in the occurrence of nephrotic syndrome.
Authors:
Mika Ikebe; Hiroshi Nonoguchi; Yushi Nakayama; Yuka Tashima; Kohei Shimada; Kazuhiko Tanzawa; Kimio Tomita
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nephron. Experimental nephrology     Volume:  94     ISSN:  1660-2129     ISO Abbreviation:  Nephron Exp. Nephrol.     Publication Date:  2003  
Date Detail:
Created Date:  2003-09-15     Completed Date:  2006-04-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101159770     Medline TA:  Nephron Exp Nephrol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  e137-45     Citation Subset:  IM    
Copyright Information:
Copyright 2003 S. Karger AG, Basel
Affiliation:
Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aspartic Acid Endopeptidases / genetics,  metabolism,  physiology*
Atrial Natriuretic Factor / metabolism
Cyclic GMP / biosynthesis
Endothelin-1 / biosynthesis,  genetics,  metabolism
Endothelin-3 / metabolism
Enzyme Induction / genetics
Gene Expression Regulation, Enzymologic / genetics
Kidney Glomerulus / enzymology
Male
Metalloendopeptidases / genetics,  metabolism,  physiology*
Nephrons / enzymology,  metabolism,  pathology
Nephrotic Syndrome / blood,  enzymology*,  metabolism,  urine
Proteinuria / chemically induced
Puromycin Aminonucleoside / adverse effects
RNA, Messenger / biosynthesis,  genetics
Rats
Rats, Sprague-Dawley
Receptors, Endothelin / antagonists & inhibitors
Sulfonamides / pharmacology
Time Factors
Chemical
Reg. No./Substance:
0/Endothelin-1; 0/Endothelin-3; 0/RNA, Messenger; 0/Receptors, Endothelin; 0/Sulfonamides; 147536-97-8/bosentan; 58-60-6/Puromycin Aminonucleoside; 7665-99-8/Cyclic GMP; 85637-73-6/Atrial Natriuretic Factor; EC 3.4.23.-/Aspartic Acid Endopeptidases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.71/endothelin-converting enzyme

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


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