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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

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

N. D. Vaziri, Y. Bai, Z. Ni, Y. Quiroz, R. Pandian and B. Rodriguez-Iturbe
Journal of Pharmacology and Experimental Therapeutics October 2007, 323 (1) 85-93; DOI: https://doi.org/10.1124/jpet.107.123638
N. D. Vaziri
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Y. Bai
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Z. Ni
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Y. Quiroz
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R. Pandian
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B. Rodriguez-Iturbe
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Abstract

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 κB (NFκB), 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 (gp91phox, p22phox, and P47phox; 20–40%), COX-2 (250%), 12-lipooxygenase (100%), MCP-1 (400%), and PAI-1 (>20-fold), activation of NFκB, 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.

Footnotes

  • This study was supported in part by a grant from the National Institutes of Health (RO1-HL0792-04).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.107.123638.

  • ABBREVIATIONS: RAS, renin angiotensin system; Ang II, angiotensin II; AT1r, angiotensin type 1 receptor; COX, cyclooxygenase; LO, lipooxygenase; MCP-1, monocyte chemoattractant protein-1; PAI-1, plasminogen activator inhibitor-1; NFκB, nuclear factor κB; phospho-IκB, phosphorylated inhibitor of NFκB; CRF, untreated 5/6 nephrectomized; NOX, NAD(P)H oxidase; 12(S)-HETE, 12(S)-hydroxyeicosatetraenoic acid; Nx, nephrectomized; ROS, reactive oxygen species; ARB, AT1 receptor blocker.

    • Received April 3, 2007.
    • Accepted July 13, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 377 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 377, Issue 2
1 May 2021
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

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

N. D. Vaziri, Y. Bai, Z. Ni, Y. Quiroz, R. Pandian and B. Rodriguez-Iturbe
Journal of Pharmacology and Experimental Therapeutics October 1, 2007, 323 (1) 85-93; DOI: https://doi.org/10.1124/jpet.107.123638

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

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

N. D. Vaziri, Y. Bai, Z. Ni, Y. Quiroz, R. Pandian and B. Rodriguez-Iturbe
Journal of Pharmacology and Experimental Therapeutics October 1, 2007, 323 (1) 85-93; DOI: https://doi.org/10.1124/jpet.107.123638
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