title: Glomerular mRNA expression of angiotensinase A after renal ablation.
abstract: The local concentration of angiotensin II (ANG II) in the renal microenvironment is not only controlled by the generation of this peptide but also by its enzymatic degradation. Angiotensinase A (ATA; aminopeptidase A, A.C.3.4.11.7) is a major exopeptidase of the glomerulus involvement in the metabolism of ANG II. We studied the glomerular mRNA levels of ATA in a remnant kidney model 1-12 weeks after 1 1/3 nephrectomy. Functional parameters (systolic blood pressure and albuminuria) demonstrated the progression of renal disease in this model. Glomerular ATA enzyme activity significantly increased 1-5 weeks after nephrectomy and returned to control levels 12 weeks after ablation. In general, changes in steady-state mRNA expression for ATA were rather small. mRNA expression for ATA in isolated glomeruli as evaluated by northern blots was slightly increased 1 and 3 weeks after 1 1/3 nephrectomy but was suppressed 5 and 12 weeks after renal ablation compared to age-matched 2-kidney controls. Treatment of animals with the ACE inhibitor ramipril for 5 and 12 weeks partly inhibited the decrease in ATA transcripts after 1 1/3 nephrectomy and stimulated expression in 2-kidney controls whereas the ACE inhibitor decreased glomerular ATA enzyme activity in nephrectomized rats at 5 weeks. Isolated glomeruli from normal controls superfused with 10(-6) M ANG II for 60 min demonstrated no change in ATA transcripts. Our results show that ATA steady-state mRNA levels are slightly elevated early (1-3 weeks) after renal ablation, and are subsequently suppressed (5-12 weeks). ATA enzyme activity is also increased early and returned (12 weeks) to levels measured in age-matched 2-kidney controls.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Hamburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wolf
authors.forename: F
authors.initials: F
authors.lastname: Thaiss
authors.forename: E
authors.initials: E
authors.lastname: Mueller
authors.forename: M
authors.initials: M
authors.lastname: Disser
authors.forename: R
authors.initials: R
authors.lastname: Pooth
authors.forename: G
authors.initials: G
authors.lastname: Zahner
authors.forename: R A
authors.initials: RA
authors.lastname: Stahl
mesh_terms: D000419:Albuminuria; D000626:Aminopeptidases / Q000235:genetics* / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D015152:Blotting, Northern; D005246:Feedback; D015870:Gene Expression; D043384:Glutamyl Aminopeptidase; D007678:Kidney Glomerulus / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D009392:Nephrectomy; D012333:RNA, Messenger / Q000378:metabolism*; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D000804:Angiotensin II; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; D012083:Renin; D017257:Ramipril