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We have previously shown that enalapril, when given acutely to renovascular patients, exerted a dose-dependent hypotensive effect. To address the same problem in chronically treated essential hypertensives, we studied 116 uncomplicated essential hypertensives, whose diastolic blood pressure was greater than or equal to 95 mm Hg at the end of a two-week placebo run-in period (time 0). According to a randomized crossover design, these patients received three doses (10, 20, or 40 mg) of enalapril qd and a placebo, each treatment being given for one month. At the end of each treatment period as well as at time 0, blood pressure and heart rate were measured 24 hours after the last dosing. In spite of a two-week run-in placebo period, placebo treatment further and significantly reduced blood pressure; however enalapril further and significantly reduced blood pressure when compared to placebo. Although absolute blood pressure values after 40 mg of enalapril were significantly lower than those after 10 mg of enalapril the relevance of this difference, mainly when compared to placebo, seems to be inconsistent. Taken together these data suggest that the hypotensive effect of enalapril chronically given to essential hypertensives and measured 24 hours after last dosing, is dose independent.
Salvetti et al. (1989) studied this question.