Glomerular mRNA expression of angiotensinase A after renal ablation

• Published in: Experimental nephrology Vol. 3; no. 4; p. 240
• Main Authors: Wolf, G, Thaiss, F, Mueller, E, Disser, M, Pooth, R, Zahner, G, Stahl, R A
• Format: Journal Article
• Language: English
• Published: Switzerland 01.07.1995
• Subjects: Albuminuria; Aminopeptidases - genetics; Aminopeptidases - metabolism; Angiotensin II - metabolism; Angiotensin II - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Blood Pressure; Blotting, Northern; Feedback; Gene Expression; Glutamyl Aminopeptidase; Kidney Glomerulus - enzymology; Kinetics; Male; Nephrectomy; Ramipril - pharmacology; Rats; Rats, Wistar; Renin - blood; RNA, Messenger - metabolism
• ISSN: 1018-7782

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.