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Cyclooxygenase‐1 derived prostaglandins are involved in the maintenance of renal function in rats with cirrhosis and ascites
Author(s) -
LópezParra Marta,
Clària Joan,
Planagumà Anna,
Titos Esther,
Masferrer Jaime L,
Woerner B Mark,
Koki Alane T,
Jiménez Wladimiro,
Altuna Rosario,
Arroyo Vicente,
Rivera Francisca,
Rodés Joan
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704528
Subject(s) - endocrinology , medicine , renal function , ascites , furosemide , cirrhosis , cyclooxygenase , kidney , renal blood flow , diuretic , celecoxib , chemistry , biochemistry , enzyme
The maintenance of renal function in decompensated cirrhosis is highly dependent on prostaglandins (PGs). Since PG synthesis is mediated by cyclooxygenase‐1 and −2 (COX‐1 and COX‐2), the present study was designed to examine which COX isoform is involved in this phenomenon. Renal COX‐1 and COX‐2 protein expression and distribution were analysed by Western blot and immunohistochemistry in nine rats with carbon tetrachloride‐induced cirrhosis and ascites and 10 control animals. The effects of placebo and selective COX‐1 (SC‐560) and COX‐2 (celecoxib) inhibitors on urine flow (V), urinary excretion of sodium (U Na V) and PGE 2 (U PGE2 V), glomerular filtration rate (GFR), renal plasma flow (RPF), the diuretic and natriuretic responses to furosemide and renal water metabolism were assessed in 88 rats with cirrhosis and ascites. COX‐1 protein levels were found to be unchanged in kidneys from cirrhotic rats. In contrast, these animals showed enhanced renal COX‐2 protein expression which was focally increased in the corticomedullary region. Although U PGE2 V was equally reduced by SC‐560 and celecoxib, only SC‐560 produced a significant decrease in U Na V, GFR and RPF and a pronounced impairment in the diuretic and natriuretic responses to furosemide in rats with cirrhosis and ascites. Neither SC‐560 nor celecoxib affected renal water metabolism in cirrhotic rats. These results indicate that despite abundant renal COX‐2 protein expression, the maintenance of renal function in cirrhotic rats is mainly dependent on COX‐1‐derived prostaglandins.British Journal of Pharmacology (2002) 135 , 891–900; doi: 10.1038/sj.bjp.0704528