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Angiotensin converting enzyme inhibitor modulates glomerular function and structure by distinct mechanisms
1Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Kidney International
|February 1, 1994
Summary
Early-phase proteinuria in puromycin aminonucleoside (PAN) nephrosis is reduced by angiotensin I converting enzyme inhibitors (ACEI) via bradykinin, not angiotensin II (Ang II). Later glomerulosclerosis progression involves Ang II.
Area of Science:
- Nephrology
- Pharmacology
- Physiology
Background:
- Puromycin aminonucleoside (PAN) nephrosis is a model for glomerular disease.
- Understanding the roles of the renin-angiotensin system (RAS) and bradykinin in nephrotic syndrome is crucial.
Purpose of the Study:
- To investigate the mechanisms underlying early-phase proteinuria and later glomerulosclerosis progression in PAN nephrosis.
- To differentiate the roles of angiotensin II (Ang II) and bradykinin in the therapeutic effects of ACE inhibitors (ACEI).
Main Methods:
- Rats with PAN nephrosis were treated with ACEI or Angiotensin II Type 1 Receptor Antagonist (Ang II RA) during the early phase or later stages.
- Bradykinin antagonist was used to assess the role of bradykinin in ACEI's effect.
- Renal biopsies were performed to assess glomerulosclerosis progression.
Main Results:
- Early-phase proteinuria in PAN rats was significantly attenuated by ACEI but not Ang II RA.
- ACEI's antiproteinuric effect was partially mediated by bradykinin.
- Neither ACEI nor Ang II RA prevented glomerulosclerosis during the acute phase.
- Later treatment with ACEI or Ang II RA ameliorated or reversed glomerulosclerosis and prevented proteinuria.
Conclusions:
- Early proteinuria in PAN nephropathy is independent of Ang II.
- The antiproteinuric effect of ACEI in early PAN nephrosis involves bradykinin activation.
- Later glomerulosclerosis progression in PAN nephrosis is driven by endogenous Ang II actions.