This study was conducted to examine whether
imidaprilat, an active diacid of the
angiotensin-converting enzyme (
ACE) inhibitor imidapril, preferentially inhibits
angiotensin I degradation rather than
bradykinin degradation, and whether
imidapril is less active than other
ACE inhibitors in inducing
cough in patients with
hypertension. The effect of
imidaprilat on the inhibition of pressor response to
angiotensin I and augmentation of depressor response to
bradykinin was compared with that of
enalaprilat and
captopril in anesthetized rats. To determine the incidence of
cough associated with
imidapril, patients with a history of
ACE inhibitor-induced dry
cough were enrolled in a randomized, open-labeled, crossover trial with two 6-week periods to be treated with
imidapril or
amlodipine, a
calcium-channel blocker. The recurrence of
cough was assessed during both treatments. In the animal study, there were no significant differences in the ratio of inhibition of pressor response to
angiotensin I and the augmentation of depressor response to
bradykinin among the
ACE inhibitors. In the
cough-challenge trial, a total of 60 patients with
hypertension were enrolled in the study.
Cough and
cough related symptoms recurred in 98.3% of the patients (59/ 60) during
imidapril therapy. In contrast, only two patients reported
cough during treatment with
amlodipine. These results indicate that
imidapril has no selectivity in inhibiting
angiotensin I- and
bradykinin-degradation in rats, and that clinically it is not different from other
ACE inhibitors in inducing
cough in patients with
hypertension.