Effect of the Ace Inhibitor Ceronapril on Cerebral Blood flow in Hypertensive Patients

OBJECTIVE: To assess the effect of the angiotensin-converting enzyme inhibitor ceronapril on cerebral blood flow (CBF) in patients with moderate hypertension. DESIGN: Patients received chlorthalidone 25 mg for 4 weeks, and if diastolic blood pressure remained in the range of 100-115 mm Hg, they were given titrated doses of ceronapril (10-40 mg/d based on blood pressure response) in addition to chlorthalidone for 9 weeks. SETTING: Outpatient research clinic. SUBJECTS: Eligible patients had moderate essential hypertension (diastolic blood pressure 100-115 mm Hg) assessed when the patients were receiving no medications. Thirteen patients were entered into the study; 1 withdrew for reasons unrelated to the study drug. Twelve patients (11 men, 1 woman; mean age 52 y) completed the study. INTERVENTION: Ceronapril, given with chlorthalidone. MAIN OUTCOME MEASURES: CBF measurements were taken at the start and end of ceronapril therapy using intravenous 133Xe; blood pressures were determined weekly. RESULTS: Mean arterial blood pressure decreased from 130 +/- 4 to 120 +/- 7 mm Hg after 4 weeks of chlorthalidone administration, and fell further to 108 +/- 8 mm Hg after an additional 9 weeks of combined chlorthalidone-ceronapril therapy (p < 0.05). CBF fell from 44 +/- 15 to 34 +/- 5 mL/min/100 g during the 9 weeks of combined therapy (p = 0.05). No adverse effects consistent with decreased CBF were observed. The decrease in CBF was not linearly correlated with the change in systemic blood pressure, but was strongly correlated (r = -0.937; p < 0.001) with the initial CBF. CONCLUSIONS: The decrease in mean arterial blood pressure was not associated with a decrease in CBF. Patients with high CBF may be predisposed to a decrease in CBF when treated with ceronapril and chlorthalidone.