title: Renal expression of aminopeptidase A in rats with two-kidney, one-clip hypertension.
abstract: BACKGROUND
  Angiotensin II (ANG II) is a major factor involved in the progression of chronic renal disease. Although the generation of this vasoactive peptide has been investigated in great detail, only a few studies have hitherto addressed the metabolism of ANG II into fragments such as angiotensin III and IV (ANG III, IV) which may exert physiological effects independent of ANG II. Aminopeptidase A (APA) is the major enzyme degrading ANG II. The aim of the current study was to evaluate glomerular APA expression in rats with two-kidney, one-clip hypertension.
  
  
  METHODS
  The left renal artery was restricted with a 0.2-mm silver clip. Kidneys were harvested 1 and 4 weeks after surgery. APA enzyme and protein expression was evaluated in kidney sections. Total APA enzyme activity and mRNA expression was assessed in isolated glomeruli. Degradation of exogenous ANG II by isolated glomeruli was measured with reverse-phase high-performance liquid chromatography.
  
  
  RESULTS
  APA enzyme activity, protein, and mRNA expression were stimulated in the clipped kidney 1 week after surgery compared with the contralateral kidney or normal controls. In contrast, 4 weeks after clipping APA activity and expression was higher in the contralateral kidney. In parallel to these findings, degradation of ANG II was greatest in isolated glomeruli obtained from the clipped kidney after 1 week. However, preparations from the contralateral kidney 4 weeks after surgery were more active in the metabolism of exogenous ANG II.
  
  
  CONCLUSIONS
  The present study provides evidence that APA is complexly regulated in in vivo situations with an activated local renin-ANG II system. ANG II appears to play a direct role in this regulation. However, since conversion of ANG II to ANG III by APA is the initial step leading to the formation of ANG IV which may exert detrimental effects not mediated through classical ANG II receptors, a local increase in APA activity may contribute to the progression of chronic renal disease even during complete AT(1)-receptor blockade.
authors.affiliation: Department of Medicine, Division of Nephrology and Osteology, University of Hamburg, Hamburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wolf
authors.forename: U
authors.initials: U
authors.lastname: Wenzel
authors.forename: K J
authors.initials: KJ
authors.lastname: Assmann
authors.forename: R A
authors.initials: RA
authors.lastname: Stahl
mesh_terms: D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D043384:Glutamyl Aminopeptidase; D006651:Histocytochemistry; D006978:Hypertension, Renovascular / Q000097:blood / Q000201:enzymology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D007678:Kidney Glomerulus / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012083:Renin / Q000097:blood
chemical_list: D012333:RNA, Messenger; D000804:Angiotensin II; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; D012083:Renin