Glomerular mRNA expression of angiotensinase A after renal ablation.
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)
Wolf
G
G
Department of Medicine, University of Hamburg, Germany.
Thaiss
F
F
Mueller
E
E
Disser
M
M
Pooth
R
R
Zahner
G
G
Stahl
R A
RA
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D000804:Angiotensin II; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; D012083:Renin; D017257:Ramipril