title: Cyclooxygenase-1 derived prostaglandins are involved in the maintenance of renal function in rats with cirrhosis and ascites.
abstract: 1. 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. 2. 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. 3. 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. 4. 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.
authors.affiliation: DNA Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona 08036, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: López-Parra
authors.forename: Joan
authors.initials: J
authors.lastname: Clària
authors.forename: Anna
authors.initials: A
authors.lastname: Planagumà
authors.forename: Esther
authors.initials: E
authors.lastname: Titos
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Masferrer
authors.forename: B Mark
authors.initials: BM
authors.lastname: Woerner
authors.forename: Alane T
authors.initials: AT
authors.lastname: Koki
authors.forename: Wladimiro
authors.initials: W
authors.lastname: Jiménez
authors.forename: Rosario
authors.initials: R
authors.lastname: Altuna
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
authors.forename: Francisca
authors.initials: F
authors.lastname: Rivera
authors.forename: Joan
authors.initials: J
authors.lastname: Rodés
mesh_terms: D000818:Animals; D001201:Ascites / Q000378:metabolism* / Q000503:physiopathology*; D015153:Blotting, Western; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000503:physiopathology; D000068579:Celecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D014867:Water / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004232:Diuretics; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D014867:Water; D005665:Furosemide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D000068579:Celecoxib