Humoral effects of long-term oral enalapril therapy

Twenty-seven subjects with essential hypertension were prospectively followed for a minimum of 100 weeks, receiving either enalapril monotherapy or enalapril and hydrochlorothiazide combination therapy. Blood pressure and the renin-angiotensin-aldosterone system were assessed following 4 weeks of placebo therapy, and 56 and 96 weeks of maintenance drug therapy. Blood pressure was well controlled with either form of therapy. Plasma renin activity remained stimulated following both long-term monotherapy and combination therapy. However, immunoreactive plasma angiotensin II concentration was not suppressed following either long-term monotherapy or combination therapy. Similarly, plasma aldosterone concentration was not suppressed following either form of therapy; indeed, combination therapy was associated with stimulation of plasma aldosterone concentration. We conclude that enalapril monotherapy or enalapril/hydrochlorothiazide therapy was effective in controlling blood pressure, but that long-term blood pressure control must be related to an angiotensin II independent antihypertensive mechanism.