부산대학교 도서관

Since a single dose of the angiotensin-converting enzyme inhibitor enalapril was shown to cause natriuresis in cirrhosis in a previous study, we investigated whether repeated doses of this substance would sustain a favorable renal effect in cirrhosis. Ten milligrams of enalapril maleate were administered once a day for 8 days to ten patients with non-azotemic cirrhosis and ascites. Enalapril reduced blood pressure significantly at 4 to 12 h (systolic blood pressure) and 2, 6, and 8 h (diastolic blood pressure) on day 2, compared to pretreatment (day 0) values, but this depressor effect decreased on day 8. No change in heart rate could be detected. Enalapril significantly suppressed serum angiotensin-converting enzyme activity and plasma aldosterone concentration (p<0.001 to 0.01), which were elevated prior to treatment, with pretreatment values of 25.8±1.8 IU/1 for serum angiotensin-converting enzyme activity and 241±67 pg/ml for plasma aldosterone concentration. This drug caused a 12 to 24% increase (p<0.05 to 0.01) in mean daily urinary volume and a 40 to 54% increase (p<0.001 to 0.01) in mean daily urinary sodium excretion from the respective pretreatment baselines during the 8-day period. Creatinine clearance was improved (p<0.05) by the treatment, with mean improvement values from 24 to 34% above the pretreatment value of 47.4±4.3 ml/min. Daily urinary prostaglandin E2, 6-keto-prostaglandin F1α, and kallikrein excretion were also significantly increased (p<0.05 to 0.01) by enalapril, with maximal increments of 101% for prostaglandin E2on day 8, 53% for 6-keto-prostaglandin F1αon day 6, and 64% for kallikrein on day 2. Enalapril thus seems to exert a therapeutic effect on renal sodium retention in patients with non-azotemic cirrhosis and ascites, with consequent improvement in renal function. This improvement after enalapril treatment may have been due in part to an activation of the bradykinin-prostaglandin system in cirrhosis.