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This Article Full Text Full Text (PDF) All Versions of this Article: 286/5/F945    most recent 00238.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Gonçalves, A. R. R. Articles by Zatz, R. Search for Related Content PubMed PubMed Citation Articles by Gonçalves, A. R. R. Articles by Zatz, R.

Renal expression of COX-2, ANG II, and AT₁ receptor in remnant kidney: strong renoprotection by therapy with losartan and a nonsteroidal anti-inflammatory

¹Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, 01246-903 São Paulo; and ²Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 13081-970 Campinas, Brazil

Submitted 1 July 2003 ; accepted in final form 12 December 2003

Chronic renal injury can be mediated by angiotensin II (ANG II) and prostanoids through hemodynamic and inflammatory mechanisms and attenuated by individual suppression of these mediators. In rats with renal ablation (Nx), we investigated 1) the intrarenal distribution of COX-2, ANG II, and the AT₁ receptor (AT₁R); 2) the renoprotective and antiinflammatory effects of an association between the AT₁R blocker, losartan (Los), and the gastric sparing anti-inflammatory nitroflurbiprofen (NOF). Adult male Munich-Wistar rats underwent Nx or sham operation (S), remaining untreated for 30 days, after which renal structure was examined in 12 Nx rats (Nx_pre). The remaining rats were followed during an additional 90 days, distributed among 4 treatment groups: Nx_V (vehicle), Nx_Los (Los), Nx_NOF (NOF), and Nx_Los/NOF (Los/NOF). Nx_pre rats exhibited marked albuminuria, hypertension, glomerulosclerosis, interstitial expansion, and macrophage infiltration, accompanied by abnormal glomerular, vascular, and interstitial COX-2 expression. ANG II appeared in interstitial cells, in contrast to S, in which ANG II was virtually confined to afferent arterioles. Intrarenal AT₁R distribution shifted from mostly tubular in S to predominantly interstitial in Nx_pre. All these changes were aggravated at 120 days and attenuated by Los and NOF monotherapies. Los/NOF treatment arrested renal structural injury and ANG II expression and reversed hypertension, albuminuria, and renal inflammation. In conclusion, abnormal expression of COX-2, ANG II, and AT₁R may be key to development of renal injury in Nx. Concomitant COX-2 inhibition and AT₁R blockade arrested renal injury and may represent a useful strategy in the treatment of chronic nephropathies.

prostaglandin-endoperoxide synthase; angiotensin II; anti-inflammatory agents; kidney failure; chronic; inflammation

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