AJP - Renal Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol 292: F861-F867, 2007. First published October 10, 2006; doi:10.1152/ajprenal.00252.2006
0363-6127/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/2/F861    most recent
00252.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hayden, M. R.
Right arrow Articles by Sowers, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hayden, M. R.
Right arrow Articles by Sowers, J. R.

Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat

Melvin R. Hayden,1 Nazif A. Chowdhury,1 Shawna A. Cooper,1 Adam Whaley-Connell,1,4 Javad Habibi,1 Lauren Witte,1 Charles Wiedmeyer,5 Camila Margarita Manrique,1 Guido Lastra,1 Carlos Ferrario,7 Craig Stump,1,2,3,6 and James R. Sowers1,2,3,6

Departments of 1Internal Medicine and 2Medical Pharmacology and Physiology and Divisions of 3Endocrinology and 4Nephrology, School of Medicine, and 5College of Veterinary Medicine, University of Missouri, and 6Harry S. Truman Veterans Affairs Medical Center, Columbia, Missouri; and 7Hypertension and Vascular Disease Unit, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina

Submitted 5 July 2006 ; accepted in final form 2 October 2006

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-beta-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-beta-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.

angiotensin II; malondialdehyde; proximal tubule cell; TG(mRen2)27 transgenic rat


Address for reprint requests and other correspondence: J. R. Sowers, Diabetes Research Program, 1656 E. Mable St., PO Box 245218, Tucson, AZ 85724-5218 (e-mail: sowersj{at}email.arizona.edu)




This article has been cited by other articles:


Home page
 HypertensionHome page
A. Whaley-Connell, J. Habibi, R. Nistala, S. A. Cooper, P. R. Karuparthi, M. R. Hayden, N. Rehmer, V. G. DeMarco, B. T. Andresen, Y. Wei, et al.
Attenuation of NADPH Oxidase Activation and Glomerular Filtration Barrier Remodeling With Statin Treatment
Hypertension, February 1, 2008; 51(2): 474 - 480.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. A. Cooper, A. Whaley-Connell, J. Habibi, Y. Wei, G. Lastra, C. Manrique, S. Stas, and J. R. Sowers
Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance
Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2009 - H2023.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. Whaley-Connell, G. Govindarajan, J. Habibi, M. R. Hayden, S. A. Cooper, Y. Wei, L. Ma, M. Qazi, D. Link, P. R. Karuparthi, et al.
Angiotensin II-mediated oxidative stress promotes myocardial tissue remodeling in the transgenic (mRen2) 27 Ren2 rat
Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E355 - E363.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.