Effects of enalapril, a new converting enzyme inhibitor, in hypertension

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Abstract
The new angiotensin-converting enzyme inhibitor, enalapril maleate, was given in single oral doses of 2.5, 5 and 10 mg to 11 hospitalized patients with uncomplicated essential hypertension who were on a 150-meq Na diet. All doses of enalapril induced reduction of mean seated diastolic blood pressure (SDBP). The magnitude of the initial SDBP reduction was not dose related, but the duration of effect was longer (> 12 h) after the 5 and 10 mg. After dosing, mean plasma angiotensin converting enzyme activity (ACE) and aldosterone concentration (PAC) fell, while plasma renin activity (PRA) rose. Serum concentrations of the active diacid form of enalapril increased linearly with dosage; ACE was inhibited maximally at concentrations above 10 ng/ml. During repeated dosing in the outpatient trial there was attenuation of the antihypertensive effect (12-24 h after dosing) in 8 of 10 patients. Despite dose increases only 2 patients achieved SDBP control (.ltoreq. 90 mm Hg). In the 5 patients in whom 50 mg/day hydrochlorothiazide was added near the end of the trial mean SDBP was further reduced. Enalapril was well tolerated. Further studies of the drug, especially in combination with diuretic, are needed.