Cyclooxygenase‐1 derived prostaglandins are involved in the maintenance of renal function in rats with cirrhosis and ascites

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 pro...

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Published in:British journal of pharmacology 2002-02, Vol.135 (4), p.891-900
Main Authors: López‐Parra, 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
Format: Article
Language:English
Subjects:
Animals
Ascites - metabolism
Ascites - physiopathology
Biological and medical sciences
Blotting, Western
Carbon Tetrachloride Poisoning - metabolism
Carbon Tetrachloride Poisoning - physiopathology
Celecoxib
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors - pharmacology
Diuretics - pharmacology
Experimental cirrhosis
Furosemide - pharmacology
Gastroenterology. Liver. Pancreas. Abdomen
Immunohistochemistry
Isoenzymes - metabolism
Kidney - metabolism
Kidney - physiopathology
Liver Cirrhosis, Experimental - metabolism
Liver Cirrhosis, Experimental - physiopathology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Membrane Proteins
Other diseases. Semiology
Prostaglandin-Endoperoxide Synthases - metabolism
Prostaglandins - biosynthesis
Pyrazoles - pharmacology
Rats
Rats, Wistar
renal COX expression
renal function
selective COX inhibition
Sulfonamides - pharmacology
Water - metabolism
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Summary: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 (UNaV) and PGE2 (UPGE2V), 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 UPGE2V was equally reduced by SC‐560 and celecoxib, only SC‐560 produced a significant decrease in UNaV, 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
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0704528