Oxidative stress and glomerular filtration barrier injury

Role of the renin-angiotensin system in the Ren2 transgenic rat

Adam T. Whaley-Connell, Nazif A. Chowdhury, Melvin R. Hayden, Craig S Stump, Javad Habibi, Charles E. Wiedmeyer, Patricia E. Gallagher, E. Ann Tallant, Shawna A. Cooper, C. Daniel Link, Carlos Ferrario, James R. Sowers

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, manifest hypertension, and exhibit increased tissue ANG II levels and oxidative stress. Evidence indicates that elevated tissue ANG II contributes to oxidative stress, increases in glomerular macromolecular permeability, and consequent albuminuria. Furthermore, angiotensin type 1 receptor (AT1R) blockers reduce albuminuria and slow progression of renal disease. However, it is not known whether improvements in glomerular filtration barrier integrity and albuminuria during treatment are related to reductions in oxidative stress and/or kidney renin-angiotensin system (RAS) activity. To investigate the renal protective effects of AT1R blockade, we treated young (6-7 wk old) male Ren2 rats with valsartan (Ren2-V; 30 mg/kg) for 3 wk and measured urine albumin, kidney malondialdehyde (MDA), RAS component mRNAs, and NADPH oxidase subunits (gp91phox and Rac1) compared with age-matched untreated Ren2 and Sprague-Dawley (S-D) rats. Basement membrane thickness, slit pore diameter and number, and foot process base width were measured by transmission electron microscopy (TEM). Results indicate that AT1R blockade lowered systolic blood pressure (30%), albuminuria (91%), and kidney MDA (80%) in Ren2-V compared with untreated Ren2 rats. Increased slit pore number and diameter and reductions in basement membrane thickness and podocyte foot process base width were strongly associated with albuminuria and significantly improved following AT1R blockade. AT1R blockade was also associated with increased angiotensin-converting enzyme-2 and neprilysin expression, demonstrating a beneficial shift in balance of renal RAS. Thus reductions in blood pressure, albuminuria, and tissue oxidative stress with AT1R blockade were associated with improved indexes of glomerular filtration barrier integrity and renal RAS in Ren2 rats.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume291
Issue number6
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Glomerular Filtration Barrier
Transgenic Rats
Renin-Angiotensin System
Albuminuria
Angiotensin Type 1 Receptor
Oxidative Stress
Kidney
Wounds and Injuries
Valsartan
Blood Pressure
Malondialdehyde
Basement Membrane
Angiotensin II Type 1 Receptor Blockers
Neprilysin
Podocytes
NADPH Oxidase
Transmission Electron Microscopy
Renin
Sprague Dawley Rats
Disease Progression

Keywords

  • Angiotensin receptor blocker
  • Malondialdehyde
  • NADPH oxidase
  • TG(mRen2)27 rat

ASJC Scopus subject areas

  • Physiology

Cite this

Oxidative stress and glomerular filtration barrier injury : Role of the renin-angiotensin system in the Ren2 transgenic rat. / Whaley-Connell, Adam T.; Chowdhury, Nazif A.; Hayden, Melvin R.; Stump, Craig S; Habibi, Javad; Wiedmeyer, Charles E.; Gallagher, Patricia E.; Tallant, E. Ann; Cooper, Shawna A.; Link, C. Daniel; Ferrario, Carlos; Sowers, James R.

In: American Journal of Physiology - Renal Physiology, Vol. 291, No. 6, 2006.

Research output: Contribution to journalArticle

Whaley-Connell, AT, Chowdhury, NA, Hayden, MR, Stump, CS, Habibi, J, Wiedmeyer, CE, Gallagher, PE, Tallant, EA, Cooper, SA, Link, CD, Ferrario, C & Sowers, JR 2006, 'Oxidative stress and glomerular filtration barrier injury: Role of the renin-angiotensin system in the Ren2 transgenic rat', American Journal of Physiology - Renal Physiology, vol. 291, no. 6. https://doi.org/10.1152/ajprenal.00167.2006
Whaley-Connell, Adam T. ; Chowdhury, Nazif A. ; Hayden, Melvin R. ; Stump, Craig S ; Habibi, Javad ; Wiedmeyer, Charles E. ; Gallagher, Patricia E. ; Tallant, E. Ann ; Cooper, Shawna A. ; Link, C. Daniel ; Ferrario, Carlos ; Sowers, James R. / Oxidative stress and glomerular filtration barrier injury : Role of the renin-angiotensin system in the Ren2 transgenic rat. In: American Journal of Physiology - Renal Physiology. 2006 ; Vol. 291, No. 6.
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