Longitudinal study of renal prostaglandin excretion in cirrhotic rats: Relationship with the renin–aldosterone system

Abstract

1. A cross-sectional study (protocol A) was performed in 19 rats with cirrhosis, induced by carbon tetrachloride (CCl4), and ascites and in 10 control animals to assess renal prostaglandin (PG) excretion in experimental cirrhosis. In an additional group of animals, including nine rats chronically exposed to CCl4 (CCl4 rats) and six control rats, a longitudinal study (protocol B) was performed to investigate the temporal relationship between changes in renal PG excretion, the renin—aldosterone system and renal function. 2. Urinary PG excretion was assessed by specific radioimmunoassay of PGE2, PGF2α, 6-keto-PGF1α and thromboxane (TX) B2 after extraction with octadecyl silica cartridges and h.p.l.c. purification. Recoveries for each prostanoid (61 ± 8% for PGE2, 64 ± 12% for PGF2α, 65 ±11% for 6-keto-PGF1α and 66 ±17% for TXB2) were determined in every sample by adding tritiated standards, and the final values were corrected according to the individual recoveries. 3. Cirrhotic rats with ascites in protocol A showed a significantly higher plasma renin and aldosterone concentrations and urinary excretion of 6-keto-PGF1α and TXB2 than did control animals. Urinary excretion of PGE2 and PGF2α, however, was significantly reduced in cirrhotic animals as compared with controls. 4. In CCl4 rats included in protocol B, there was a close chronological relationship between the activation of the renin-aldosterone system, as estimated by urinary aldosterone excretion, the onset of sodium retention and the increase in urinary excretion of 6-keto-PGF1α and TXB2. The urinary excretion of PGE2 and PGF2α in CCl4 rats was reduced throughout the study. 5. These results suggest that in rats with CCl4-induced cirrhosis, the increased renal production of prostacyclin and TXA2 is a consequence of the stimulation of endogenous vasoconstrictor systems. The impaired urinary excretion of PGE2 and PGF2α in CCl4 rats may be secondary to an inhibitory effect of CCl4 on PG synthesis in the renal tubules.