Renal expression of COX-2, ANG II, and AT<subscript>1</subscript> receptor in remnant kidney: strong renoprotection by therapy with losartan and a nonsteroidal anti-inflammatory.
In: American Journal of Physiology: Renal Physiology, Jg. 286 (2004-05-01), S. F945- (10S.)
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Zugriff:
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 5/6 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 (Nxpre). The remaining rats were followed during an additional 90 days, distributed among 4 treatment groups: Nxv (vehicle), NxLos (Los), NXNOF (NOF), and NXLos/NOF (Los/NOF). Nxpre 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 Nxpre. 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. [ABSTRACT FROM AUTHOR]
Titel: |
Renal expression of COX-2, ANG II, and AT<subscript>1</subscript> receptor in remnant kidney: strong renoprotection by therapy with losartan and a nonsteroidal anti-inflammatory.
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Autor/in / Beteiligte Person: | Ricardo, Anderson ; Gonçalves, Roman ; Fujihara, Clarice Kazue ; Mattar, Ana Lúcia ; Malheiros, Denise Maria Avancini Costa ; Noronha, Irene de Lourdes ; de Nucci, Gilberto ; Zatz, Roberto |
Zeitschrift: | American Journal of Physiology: Renal Physiology, Jg. 286 (2004-05-01), S. F945- (10S.) |
Veröffentlichung: | 2004 |
Medientyp: | academicJournal |
ISSN: | 1931-857X (print) |
DOI: | 10.1152/ajprenal.00238.2003 |
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