Fredersdorf, Sabine and Weil, Joachim and Ulucan, Coskun and Birner, Christoph and Buettner, Roland and Schubert, Thomas and Boeger, Carsten A. and Debl, Kurt and Muders, Frank and Riegger, Guenter A. and Luchner, Andreas (2007) Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 375 (2). pp. 95-103. ISSN 0028-1298,
Full text not available from this repository. (Request a copy)Abstract
Inhibition of the renin angiotensin aldosterone system (RAAS) produces protective effects on cardio-renal injury in type 2 diabetes. Vasopeptidase inhibitors (VPI) represent a new pharmacological tool, acting by simultaneous inhibition of the RAAS and neutral endopeptidase. We examined the effects of chronic VPI on renal function and morphology in experimental type 2 diabetes as compared to angiotensin converting enzyme inhibition (ACE-I). Zucker diabetic fatty rats aged 13 weeks were treated with either VPI (AVE7688, ZDF-VPI, n=8) or ACE-I (Ramipril, ZDF-ACE-I, n=7) or placebo (ZDF, n-8). Heterozygous rats served as non-diabetic controls (Ctr, n=8). Both treatments led to a similar decrease in blood pressure. After 10 weeks of treatment, ZDF developed marked albuminuria. The latter was significantly attenuated in ZDF-VPI as compared to ZDF and ZDF-ACE-I. Renal histology revealed a significant expansion in the glomerular tuft area in all ZDF groups. However, expression of glomerular desmin, which has been recognized as a sensitive marker of early podocyte damage, was significantly increased in ZDF as compared to Ctr. Desmin was reduced in ZDF-VPI but not in animals treated with ACE-I. There was a correlation between albumin excretion and desmin-positive glomerular area. In experimental type 2 diabetes, albuminuria correlates to podocyte damage. These hallmarks of diabetic nephropathy are attenuated by VPI to a greater extent than by ACE-I alone. These findings suggest that podocyte damage is an early critical step in the progression of diabetic nephropathy, and that VPI is a promising pharmacological tool in the treatment of diabetic renal disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CONVERTING ENZYME-INHIBITION; ATRIAL-NATRIURETIC-PEPTIDE; RENAL INJURY; MESANGIAL CELLS; GLOMERULOSCLEROSIS; NEPHROPATHY; EXPRESSION; MELLITUS; HYPERTROPHY; FIBROSIS; diabetes mellitus; kidney glomerulosclerosis; vasopeptidase inhibition |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Dec 2020 08:01 |
| Last Modified: | 21 Dec 2020 08:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32987 |
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