QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.107.123638v1 323/1/85    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vaziri, N. D. Articles by Rodriguez-Iturbe, B. Search for Related Content PubMed PubMed Citation Articles by Vaziri, N. D. Articles by Rodriguez-Iturbe, B.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Intra-Renal Angiotensin II/AT₁ Receptor, Oxidative Stress, Inflammation, and Progressive Injury in Renal Mass Reduction

Division of Nephrology and Hypertension, University of California, Irvine, California (N.D.V., Y.B., Z.N., R.P.); and Renal Service, Hospital Universitario, Universidad del Zulia and Centro de Investigaciones Biomédicas, IVIC-Zulia, Maracaibo, Venezuela (Y.Q., B.R.-I.)

Significant reduction of renal mass triggers a chain of events that result in glomerular hypertension/hyperfiltration, proteinuria, glomerulosclerosis, tubulointerstitial injury, and end-stage renal disease. These events are mediated by a constellation of hemodynamic, oxidative, and inflammatory reactions that are, in part, driven by local AT₁ receptor (AT₁r) activation by angiotensin II (Ang II). Here we explored the effects of 5/6 nephrectomy with and without AT₁r blockade (losartan for 8 weeks) on AT₁r and AT₂r and Ang II-positive cell count, pathways involved in oxidative stress and inflammation [NAD(P)H oxidase, nuclear factor B (NFB), 12-lipooxygenase, cyclooxygenase (COX)-1, COX-2, monocyte chemoattractant protein (MCP)-1, plasminogen activator inhibitor (PAI)-1, renal T cell, and macrophage infiltration] as well as renal function and structure. The untreated group exhibited hypertension, deterioration of renal function and structure, reduced or unchanged plasma renin activity, aldosterone concentration, marked up-regulations of AT₁r (250%), Ang II-expressing cell count (>20-fold), NAD(P)H oxidase subunits (gp91^phox, p22^phox, and P47^phox; 20–40%), COX-2 (250%), 12-lipooxygenase (100%), MCP-1 (400%), and PAI-1 (>20-fold), activation of NFB, and interstitial infiltrations of T cells and macrophages in the remnant kidneys. AT₁r blockade attenuated the biochemical and histological abnormalities, prevented hypertension, and decelerated deterioration of renal function and structure. Thus, the study demonstrated a link between up-regulation of Ang II/AT₁r system and oxidative stress, inflammation, hypertension, and progression of renal disease in rats with renal mass reduction.

Address correspondence to: Dr. Nosratola D. Vaziri, MACP, Division of Nephrology and Hypertension, UCI Medical Center, 101 The City Drive, Bldg. 53, Rm. 125, Rt. 81, Orange, CA 92868. E-mail: ndvaziri{at}uci.edu

This article has been cited by other articles:

				G. Piecha, N. Koleganova, M.-L. Gross, A. Geldyyev, M. Adamczak, and E. Ritz Regression of glomerulosclerosis in subtotally nephrectomized rats: effects of monotherapy with losartan, spironolactone, and their combination Am J Physiol Renal Physiol, July 1, 2008; 295(1): F137 - F144. [Abstract] [Full Text] [PDF]

				Y. Quiroz, A. Ferrebuz, F. Romero, N. D. Vaziri, and B. Rodriguez-Iturbe Melatonin ameliorates oxidative stress, inflammation, proteinuria, and progression of renal damage in rats with renal mass reduction Am J Physiol Renal Physiol, February 1, 2008; 294(2): F336 - F344. [Abstract] [Full Text] [PDF]