title: Angiotensin converting-enzyme inhibition restores glomerular glycosaminoglycans in rat puromycin nephrosis.
abstract: BACKGROUND
  Aberrant glomerular polyanionic charge of glycosaminoglycans (GAGs) and sialic acid expression has been observed in proteinuric human and experimental glomerular diseases. Angiotensin-converting enzyme inhibitors (ACEI) lower proteinuria and amend renal function deterioration via hemodynamic mechanisms. We tested the hypothesis that ACEI modulate proteinuria additionally by modifying glomerular GAGs.
  
  
  METHODS
  In this study, we explored the effects of the ACEI enalapril on proteinuria and GAG synthesis in puromycin aminonucleoside (PAN)-treated rats. We employed cationic colloidal gold (CCG) localization in glomerular basement membranes (GBM) to identify GAGs by electron microscopy and determined sialic acid residues by immunohistochemical staining with lectins. To clarify ACEI effects on GAG production in vitro, we studied de novo GAG synthesis into newly synthesized proteoglycans in podocytes and mesangial cells using35S incorporation. Cells were incubated with or without PAN, and with increasing doses of the ACEI enalaprilat.
  
  
  RESULTS
  PAN rats developed severe proteinuria that was significantly improved by enalapril treatment. In non-treated PAN rats GBM GAGs were reduced, whereas in the enalapril-treated group GBM GAGs were significantly increased to control levels. Enalapril did not affect glomerular sialic acid. Furthermore, in cultured podocytes and mesangial cells PAN decreased de novo GAG synthesis, an effect which was significantly ameliorated by enalaprilat treatment.
  
  
  CONCLUSIONS
  Treatment with ACEI improves permselectivity properties of the glomerular capillary wall by maintaining its GAG content. This finding provides an additional new mechanism, whereby ACEI exert anti-proteinuric effects.
authors: Department of Nephrology, Rabin Medical Center, 7 Keren Kayemet st., Petah-Tikva, Sackler Medical School, Tel-Aviv University, Tel Aviv, Israel.
authors: Michal
authors: M
authors: Herman-Edelstein
authors: Department of Nephrology, Rabin Medical Center, 7 Keren Kayemet st., Petah-Tikva, Sackler Medical School, Tel-Aviv University, Tel Aviv, Israel.
authors: Avry
authors: A
authors: Chagnac
authors: Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors: Zvi
authors: Z
authors: Nevo
authors: Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors: Ehud
authors: E
authors: Skutelsky
authors: Department of Nephrology, Rabin Medical Center, 7 Keren Kayemet st., Petah-Tikva, Sackler Medical School, Tel-Aviv University, Tel Aviv, Israel.
authors: Yoav
authors: Y
authors: Evron
authors: Department of Nephrology, Rabin Medical Center, 7 Keren Kayemet st., Petah-Tikva, Sackler Medical School, Tel-Aviv University, Tel Aviv, Israel.
authors: Yehudit
authors: Y
authors: Hirsch
authors: Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors: Lya
authors: L
authors: Ben-Dor
authors: Department of Nephrology, Tel Aviv Medical Center, 6 Weizman st, Tel Aviv, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors: Idit
authors: I
authors: Schwartz
authors: Department of Nephrology, Tel Aviv Medical Center, 6 Weizman st, Tel Aviv, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors: Doron
authors: D
authors: Schwartz
authors: Department of Nephrology, Tel Aviv Medical Center, 6 Weizman st, Tel Aviv, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel. Electronic address: taliaw@tlvmc.gov.il.
authors: Talia
authors: T
authors: Weinstein
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D009401:Nephrosis / Q000378:metabolism* / Q000473:pathology; D050199:Podocytes / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D011692:Puromycin Aminonucleoside / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D006025:Glycosaminoglycans; D011500:Protein Synthesis Inhibitors; D011692:Puromycin Aminonucleoside; D004656:Enalapril
keywords: ACE inhibitors; Glycosaminoglycans; Proteinuria; Puromycin