Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat

Melvin R. Hayden, Nazif A. Chowdhury, Shawna A. Cooper, Adam Whaley-Connell, Javad Habibi, Lauren Witte, Charles Wiedmeyer, Camila Margarita Manrique, Guido Lastra, Carlos Ferrario, Craig S Stump, James R. Sowers

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5-8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6-7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-D-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and X60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats (P < 0.05) correlated strongly with albuminuria (r2 = 0.83) and moderately with MDA (r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats (P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-D-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume292
Issue number2
DOIs
StatePublished - Feb 2007

Fingerprint

Transgenic Rats
Albuminuria
Microvilli
Valsartan
Malondialdehyde
Blood Pressure
Sprague Dawley Rats
Hexosaminidases
Oxidative Stress
Placebos
Albumins
Transmission Electron Microscopy
Renin
Catalase
Lipid Peroxidation
Therapeutics
Staining and Labeling
Hypertension
Kidney

Keywords

  • Angiotensin II
  • Malondialdehyde
  • Proximal tubule cell
  • TG(mRen2)27 transgenic rat

ASJC Scopus subject areas

  • Physiology

Cite this

Hayden, M. R., Chowdhury, N. A., Cooper, S. A., Whaley-Connell, A., Habibi, J., Witte, L., ... Sowers, J. R. (2007). Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat. American Journal of Physiology - Renal Physiology, 292(2). https://doi.org/10.1152/ajprenal.00252.2006

Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat. / Hayden, Melvin R.; Chowdhury, Nazif A.; Cooper, Shawna A.; Whaley-Connell, Adam; Habibi, Javad; Witte, Lauren; Wiedmeyer, Charles; Manrique, Camila Margarita; Lastra, Guido; Ferrario, Carlos; Stump, Craig S; Sowers, James R.

In: American Journal of Physiology - Renal Physiology, Vol. 292, No. 2, 02.2007.

Research output: Contribution to journalArticle

Hayden, MR, Chowdhury, NA, Cooper, SA, Whaley-Connell, A, Habibi, J, Witte, L, Wiedmeyer, C, Manrique, CM, Lastra, G, Ferrario, C, Stump, CS & Sowers, JR 2007, 'Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat', American Journal of Physiology - Renal Physiology, vol. 292, no. 2. https://doi.org/10.1152/ajprenal.00252.2006
Hayden, Melvin R. ; Chowdhury, Nazif A. ; Cooper, Shawna A. ; Whaley-Connell, Adam ; Habibi, Javad ; Witte, Lauren ; Wiedmeyer, Charles ; Manrique, Camila Margarita ; Lastra, Guido ; Ferrario, Carlos ; Stump, Craig S ; Sowers, James R. / Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat. In: American Journal of Physiology - Renal Physiology. 2007 ; Vol. 292, No. 2.
@article{5b7114755cd348e9860cd60b0a393ca9,
title = "Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat",
abstract = "TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5-8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6-7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-D-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and X60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats (P < 0.05) correlated strongly with albuminuria (r2 = 0.83) and moderately with MDA (r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats (P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-D-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.",
keywords = "Angiotensin II, Malondialdehyde, Proximal tubule cell, TG(mRen2)27 transgenic rat",
author = "Hayden, {Melvin R.} and Chowdhury, {Nazif A.} and Cooper, {Shawna A.} and Adam Whaley-Connell and Javad Habibi and Lauren Witte and Charles Wiedmeyer and Manrique, {Camila Margarita} and Guido Lastra and Carlos Ferrario and Stump, {Craig S} and Sowers, {James R.}",
year = "2007",
month = "2",
doi = "10.1152/ajprenal.00252.2006",
language = "English (US)",
volume = "292",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat

AU - Hayden, Melvin R.

AU - Chowdhury, Nazif A.

AU - Cooper, Shawna A.

AU - Whaley-Connell, Adam

AU - Habibi, Javad

AU - Witte, Lauren

AU - Wiedmeyer, Charles

AU - Manrique, Camila Margarita

AU - Lastra, Guido

AU - Ferrario, Carlos

AU - Stump, Craig S

AU - Sowers, James R.

PY - 2007/2

Y1 - 2007/2

N2 - TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5-8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6-7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-D-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and X60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats (P < 0.05) correlated strongly with albuminuria (r2 = 0.83) and moderately with MDA (r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats (P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-D-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.

AB - TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5-8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6-7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-D-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and X60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats (P < 0.05) correlated strongly with albuminuria (r2 = 0.83) and moderately with MDA (r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats (P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-D-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.

KW - Angiotensin II

KW - Malondialdehyde

KW - Proximal tubule cell

KW - TG(mRen2)27 transgenic rat

UR - http://www.scopus.com/inward/record.url?scp=33846886531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846886531&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00252.2006

DO - 10.1152/ajprenal.00252.2006

M3 - Article

C2 - 17032939

AN - SCOPUS:33846886531

VL - 292

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 2

ER -