Unmasking of the hypotensive effect of nifedipine in normotensives by addition of the angiotensin converting enzyme inhibitor benazepril

Abstract

Objective: To study the pharmacological interaction between a dihydropyridine derivative (nifedipine slow release 20 mg) and inhibition of the renin-angiotensin system (benazepril 10 mg).

Design: Single application at intervals of 2 weeks in an open-label three-way cross-over design.

Setting: Institutional pharmacological unit.

Participants: Nine healthy male volunteers.

Main outcome measures(s): Blood pressure and heart rate were recorded in the supine position for 24 h as well as plasma drug levels, plasma angiotensin converting enzyme activity and active plasma renin concentration.

Results: Nifedipine increased active plasma renin two-fold and benazepril increased it five-fold. The combination of the two drugs accelerated the increase of active renin during the first 2 h after drug intake. Whereas no hypertensive effect could be detected after nifedipine or benazepril alone, a significant fall in systolic and diastolic blood pressure was observed for up to 9 to 12 h after the combination. The increase in heart rate induced by nifedipine was minimized by the addition of benazepril. There was no interaction between the pharmacokinetics of benazeprilate and nifedipine which would explain these pharmacodynamic effects.

Conclusion: These results demonstrate that, in normotensive volunteers, the renin-angiotensin system contributes to mask the hypotensive effect of a single oral dose of dihydropiridine. The concomitant administration of a converting enzyme inhibitor discloses the hypotensive effect and limits the baroreflex-mediated increase in heart rate secondary to vasodilation.