Interaction of enalapril with sodium restriction, diuretics, and slow-channel calcium-blocking drugs

While monotherapy sometimes controls blood pressure (BP), it is often essential to add a second drug for adequate control. This study examined in a factorial fashion the interaction of enalapril with some commonly used antihypertensive therapies. There were between 10 and 16 patients in each study, and the patients had responded in part to the two drugs used. Enalapril and sodium restriction lowered BP 12 +/- 3/11 +/- 2 and 4 +/- 2/3 +/- 1 mm Hg, respectively. The effects of the two therapies were additive, and there was no interaction. Enalapril and hydrochlorothiazide lowered BP 11 +/- 3/8 +/- 3 and 8 +/- 2/6 +/- 2 mm Hg, respectively. The effect of the two drugs together indicated a positive interaction of 4 +/- 2/3 +/- 1 mm Hg (p less than 0.05). Enalapril and nifedipine both lowered BP (10 +/- 2/8 +/- 1 and 11 +/- 3/8 +/- 1 mm Hg). The two drugs combined had a strongly positive interaction of 10 +/- 3/7 +/- 2 mm Hg (p less than 0.001). Enalapril can be used with the other therapeutic methods tested. If a converting enzyme inhibitor does not reduce BP adequately, it appears appropriate to add a thiazide diuretic or a slow-channel calcium-blocking drug. The mechanism of the positive interaction with diuretics probably reflects an effect on the renin-angiotensin system, but the explanation for the synergism with slow-channel calcium-blocking drugs is unclear.