Plasma prostaglandin E in portal hypertension: effect of suppression by indomethacin

ABSTRACT

A possible role of vasodilating prostaglandins [PGs] in the pathogenesis of circulating abnormalities of cirrhosis as well as in portal hypertension and renal function status was studied. Plasma PGE [by radioimmunoassay RIA], percutaneous trans-splenic portal manometry and 24 hours creatinine clearance [CrCl] were measured in 40 males with chronic liver disease [20 ascitics and 20 non-ascitics] before and after one day oral indomethacin 50 mg/8 hours] administration. Portal pressure [PP] was graded as moderately and severely raised. Ascitics had higher plasma PGE [P < 0.001] and lower CrCl [p < 0.01] than non-ascitics. PP was not significantly different in ascitics and non-ascitics plasma PGE was not significantly different in patients with moderate compared to those with severe portal hypertension. Indomethacin induced a reduction in PGE in both ascitics [from 6.09 +/- 0.29 to 2.83 +/- 0.43 ng/ml, P < 0.01] and non ascitics [from 4.15 +/- 0.31 to 2.87 +/- 0.29 ng/ml, P<0.001] and in patients with moderate portal hypertension [from 4.85 +/- 1.06 to 2.82 +/- 0.33 ng/ml, P < 0.001] and those with severe portal hypertension [from 5.19 +/- 1.02 to 2.85 +/- 0.38 ng/ml, P < 0.001]. PP was reduced in ascitics [from 30.2 +/- 5.23 to 26.0 +/- 4.67 cm saline, P < 0.001] and non-ascitics [from 28.05 +/- 3.96 to 25.15 +/- 3.51 cm saline, P < 0.001]. CrCl was reduced in ascitics [from 98.6 +/- 7.15 to 64.8 +/- 4.9 ml/min, P < 0.001] and non ascitics [from 105.15 +/- 7.01 to 90.5 + 6.12 ml/ mill, P < 0.001]. Plasma PGE, PP. and CrCl decrements [J] were higher [P < 0.001] in ascitics than in non-ascitics [3.29 +/- 0.42 vs 1.28 +/- 0.24 ng/ml, 4.2 +/- 1.1 vs 2.9 +/- 0.91 cm saline and 33.8 +/- 0.04 vs 14.2 +/- 3.78 ml/min, respectively]. In both ascitics and non-ascitics JPGE, JP and JCrCl were positively intercorrelated [P <0.01]. Plasma PGE contributes in the pathogenesis of portal hypertension, although it does not determine its severity. PGE synthesis inhibition by indomethacin affectively reduces PP. Adversely, it reduces glomerular filtration rate especially in ascitic patients