ackground : Angiotensin converting enzyme(ACE) inhibitors are widely used for the treatment of hypertension and heart failture without serious side effects, but in some patients, they induce intractable cough. The meehanism of this cough is not
known,
but ACE and kininase Ⅱ are the same enzyme, the derangement in the metabolosm of kinines and Substance-P by ACE inhibitors has been proposed as one possibility. So we performed a placebo-controlled, double-blind, randomized crossover study, to
find out
whether the enalrpril can change the sensitivity to cansaicin which released Substance-P from the nerve ending and its relation to the development of cough after the enalarpril.
Method : The subjects were 21 patients (9 men and 12 wemen) with mild to moderate
hypertension. Eleven patients developed cough with the Enalarpril (cougher), and 10 patients
didn't have cough(non-cougher) and served as a control group. Baseline PFT, serum IgE
level, and blood eosinophil count were done. The patients received either enalarpril 10 mg per
day or placebo for one week, and after the washout period of at least one week, another
drug(placebo if the patient had enalapril previously and vice versa) was given for a week.
Blood preasure, pulmonary function test, and capsaicin challenge test were performed at the
end of each period. Capsaicin challenge test was done by inhalation of different concentration
of capsaicin vis DeVilbis 646 nebulizer with dosimeter (SCM Co, U.S.A) and the lowest
concentration which induced 2 or more coughs (Th-w) and 5 or more coughs (Th-5) were
determined.
Results : The age of the two groups were similar (55.5 vs 52 years), but females were
predominant in cougher (8 female and 4 male) compared to non-cougher (4 female and 6
male). There was no Significant difference in serum IgE level, eosinophil counts, and
pulmonary function between two groups. Cough developed immediately after the inhalation of
capsaicin, and the dose-response relationship was found between the number of coughs and
the concentration of capsaicin. In all patients, Th-2 was 19.7±16.1 uM and Th-5 was 78.8±
48.6 uM. But there was no significant difference in both Th-2 and Th-5 between coughers
(21.3 uM and 72.2 uM) and non-coughers (18.0 uM and 81.6 uM). Also, no significant change
in Th-2 and Th-5 was found during the therapy of enarlapril compared to the placebo period
in both groups. Among 11 cxoughers, 2 patients developed more coughs with capsaicin
inhalation after the enarlapril compared to placebo period (responder), and in non-cougher, 3
among 10 patients were responders. Blood pressure was significantly decreased after the
Enarlapril, but no significant change in pulmonary function was noted.
Conclusion : Our data suggest that Enarlapril does not increases the sensitivity to
capsaicin and the cough after the Enarlapril seems to have different mechanism.
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