To evaluate the antihypertensive effects of lisinopril, a renally excreted angiotensin-converting enzyme inhibitor, we assessed supervised administration of the drug after hemodialysis (HD) three times weekly. Blood pressure (BP) was assessed by interdialytic 44-hour ambulatory BP (ABP) monitoring, and endocrine responses were assessed by plasma renin activity (PRA) before and after dialysis. Lisinopril dose was titrated at biweekly intervals. If this was not effective after full titration (lisinopril to 40 mg three times weekly), ultrafiltration was added to reduce dry weight. The primary outcome variable was change in BP from the end of the run-in period to the end of the study. No change in mean ABP was noted during run-in. However, mean 44-hour ABP decreased from 149 +/- 14 (SD)/84 +/- 9 to 127 +/- 16/73 +/- 9 mm Hg, a decrease of 22/11 mm Hg (P < 0.001) at final evaluation. Of 11 patients who completed the trial, only 2 patients had systolic hypertension (greater than or equal to 135 mm Hg) and 1 patient had diastolic hypertension (greater than or equal to 85 mm Hg) at the final visit. Four patients were administered 10 mg of lisinopril; 5 patients, 20 mg; and 2 patients, 40 mg; only 1 of these patients required ultrafiltration therapy. There was a persistent anti hypertensive effect over 44 hours. BP reduction was achieved without an increase in intradialytic symptomatic or asymptomatic hypotensive episodes. PRA increased in response to dialysis, as well as lisinopril. In conclusion, supervised lisinopril therapy is effective in controlling hypertension in chronic HD patients. This may be related to blockade of angiotensin 11 generation by kidneys despite the loss of excretory function. (C) 2001 by the National Kidney Foundation, Inc.