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Oxidative stress and glomerular filtration barrier injury: role of the renin-angiotensin system in the Ren2 transgenic rat.
Am J Physiol Renal Physiol. 2006 Dec; 291(6):F1308-14.AJ

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 (gp91(phox) 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.

Authors+Show Affiliations

Department of Internal Medicine, University of Missouri School of Medicine, 1 Hospital Dr., MA410 Medical Science Bldg., Columbia, MO 65212, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16788142

Citation

Whaley-Connell, Adam T., et al. "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, 2006, pp. F1308-14.
Whaley-Connell AT, Chowdhury NA, Hayden MR, et al. Oxidative stress and glomerular filtration barrier injury: role of the renin-angiotensin system in the Ren2 transgenic rat. Am J Physiol Renal Physiol. 2006;291(6):F1308-14.
Whaley-Connell, A. T., Chowdhury, N. A., Hayden, M. R., Stump, C. S., Habibi, J., Wiedmeyer, C. E., Gallagher, P. E., Tallant, E. A., Cooper, S. A., Link, C. D., Ferrario, C., & Sowers, J. R. (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, 291(6), F1308-14.
Whaley-Connell AT, et al. Oxidative Stress and Glomerular Filtration Barrier Injury: Role of the Renin-angiotensin System in the Ren2 Transgenic Rat. Am J Physiol Renal Physiol. 2006;291(6):F1308-14. PubMed PMID: 16788142.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidative stress and glomerular filtration barrier injury: role of the renin-angiotensin system in the Ren2 transgenic rat. AU - Whaley-Connell,Adam T, AU - Chowdhury,Nazif A, AU - Hayden,Melvin R, AU - Stump,Craig S, AU - Habibi,Javad, AU - Wiedmeyer,Charles E, AU - Gallagher,Patricia E, AU - Tallant,E Ann, AU - Cooper,Shawna A, AU - Link,C Daniel, AU - Ferrario,Carlos, AU - Sowers,James R, Y1 - 2006/06/20/ PY - 2006/6/22/pubmed PY - 2007/1/6/medline PY - 2006/6/22/entrez SP - F1308 EP - 14 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 291 IS - 6 N2 - 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 (gp91(phox) 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. SN - 1931-857X UR - https://www.unboundmedicine.com/medline/citation/16788142/Oxidative_stress_and_glomerular_filtration_barrier_injury:_role_of_the_renin_angiotensin_system_in_the_Ren2_transgenic_rat_ L2 - http://www.physiology.org/doi/full/10.1152/ajprenal.00167.2006?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -