PortalPublikationenVasopeptidase inhibition attenuates proteinuria and podocyte...

Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats

Standard

Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats. / Fredersdorf, Sabine; Weil, Joachim; Ulucan, Coskun; Birner, Christoph; Büttner, Roland; Schubert, Thomas; Böger, Carsten A; Debl, Kurt; Muders, Frank; Riegger, Günter A; Luchner, Andreas.

in: N-S ARCH PHARMACOL, Jahrgang 375, Nr. 2, 04.2007, S. 95-103.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Fredersdorf, S, Weil, J, Ulucan, C, Birner, C, Büttner, R, Schubert, T, Böger, CA, Debl, K, Muders, F, Riegger, GA & Luchner, A 2007, 'Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats', N-S ARCH PHARMACOL, Jg. 375, Nr. 2, S. 95-103. https://doi.org/10.1007/s00210-007-0147-9

APA

Fredersdorf, S., Weil, J., Ulucan, C., Birner, C., Büttner, R., Schubert, T., Böger, C. A., Debl, K., Muders, F., Riegger, G. A., & Luchner, A. (2007). Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats. N-S ARCH PHARMACOL, 375(2), 95-103. https://doi.org/10.1007/s00210-007-0147-9

Vancouver

Fredersdorf S, Weil J, Ulucan C, Birner C, Büttner R, Schubert T et al. Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats. N-S ARCH PHARMACOL. 2007 Apr;375(2):95-103. https://doi.org/10.1007/s00210-007-0147-9

Bibtex

@article{0ca99c5227f144e2ba6f24e6c527283c,
title = "Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats",
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.",
keywords = "Angiotensin-Converting Enzyme Inhibitors/pharmacology, Animals, Antihypertensive Agents/pharmacology, Atrial Natriuretic Factor/blood, Blood Glucose/metabolism, Blood Pressure/drug effects, Diabetes Mellitus, Experimental/blood, Heterocyclic Compounds, 3-Ring/pharmacology, Male, Microscopy, Polarization/methods, Neprilysin/antagonists & inhibitors, Podocytes/drug effects, Protease Inhibitors/pharmacology, Proteinuria/drug therapy, Ramipril/therapeutic use, Rats, Rats, Zucker, Renin-Angiotensin System/drug effects, Triglycerides/blood, Weight Gain/drug effects",
author = "Sabine Fredersdorf and Joachim Weil and Coskun Ulucan and Christoph Birner and Roland B{\"u}ttner and Thomas Schubert and B{\"o}ger, {Carsten A} and Kurt Debl and Frank Muders and Riegger, {G{\"u}nter A} and Andreas Luchner",
year = "2007",
month = apr,
doi = "10.1007/s00210-007-0147-9",
language = "English",
volume = "375",
pages = "95--103",
journal = "N-S ARCH PHARMACOL",
issn = "0028-1298",
publisher = "Springer",
number = "2",

}

RIS

TY - JOUR

T1 - Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats

AU - Fredersdorf, Sabine

AU - Weil, Joachim

AU - Ulucan, Coskun

AU - Birner, Christoph

AU - Büttner, Roland

AU - Schubert, Thomas

AU - Böger, Carsten A

AU - Debl, Kurt

AU - Muders, Frank

AU - Riegger, Günter A

AU - Luchner, Andreas

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

KW - Angiotensin-Converting Enzyme Inhibitors/pharmacology

KW - Animals

KW - Antihypertensive Agents/pharmacology

KW - Atrial Natriuretic Factor/blood

KW - Blood Glucose/metabolism

KW - Blood Pressure/drug effects

KW - Diabetes Mellitus, Experimental/blood

KW - Heterocyclic Compounds, 3-Ring/pharmacology

KW - Male

KW - Microscopy, Polarization/methods

KW - Neprilysin/antagonists & inhibitors

KW - Podocytes/drug effects

KW - Protease Inhibitors/pharmacology

KW - Proteinuria/drug therapy

KW - Ramipril/therapeutic use

KW - Rats

KW - Rats, Zucker

KW - Renin-Angiotensin System/drug effects

KW - Triglycerides/blood

KW - Weight Gain/drug effects

U2 - 10.1007/s00210-007-0147-9

DO - 10.1007/s00210-007-0147-9

M3 - SCORING: Journal article

C2 - 17333128

VL - 375

SP - 95

EP - 103

JO - N-S ARCH PHARMACOL

JF - N-S ARCH PHARMACOL

SN - 0028-1298

IS - 2

ER -