title: Regulation of endothelin-converting enzyme 1 in nephrotic syndrome in rats.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Ikebe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonoguchi
authors.forename: Yushi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tashima
authors.forename: Kohei
authors.initials: K
authors.lastname: Shimada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tanzawa
authors.forename: Kimio
authors.initials: K
authors.lastname: Tomita
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D000077300:Bosentan; D006152:Cyclic GMP / Q000096:biosynthesis; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019334:Endothelin-3 / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes; D004790:Enzyme Induction / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D007678:Kidney Glomerulus / Q000201:enzymology; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009399:Nephrons / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009404:Nephrotic Syndrome / Q000097:blood / Q000201:enzymology* / Q000378:metabolism / Q000652:urine; D011507:Proteinuria / Q000139:chemically induced; D011692:Puromycin Aminonucleoside / Q000009:adverse effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D012333:RNA, Messenger; D013449:Sulfonamides; D011692:Puromycin Aminonucleoside; D009320:Atrial Natriuretic Factor; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D006152:Cyclic GMP; D000077300:Bosentan