PT - JOURNAL ARTICLE AU - N. D. Vaziri AU - Y. Bai AU - Z. Ni AU - Y. Quiroz AU - R. Pandian AU - B. Rodriguez-Iturbe TI - Intra-Renal Angiotensin II/AT<sub>1</sub> Receptor, Oxidative Stress, Inflammation, and Progressive Injury in Renal Mass Reduction AID - 10.1124/jpet.107.123638 DP - 2007 Oct 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 85--93 VI - 323 IP - 1 4099 - http://jpet.aspetjournals.org/content/323/1/85.short 4100 - http://jpet.aspetjournals.org/content/323/1/85.full SO - J Pharmacol Exp Ther2007 Oct 01; 323 AB - 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 (&gt;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 (&gt;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. The American Society for Pharmacology and Experimental Therapeutics