OBJECTIVES We investigated whether augmentation of bradykinin (BK) bioavail
ability with angiotensin-converting enzyme (ACE) inhibition is associated w
ith reduced exercise-induced myocardial ischemia in hypertension.
BACKGROUND Bradykinin responses are depressed in hypertension, and endothel
ial dysfunction contributes to myocardial ischemia by promoting abnormal co
ronary vasomotion during stress.
METHODS Fourteen hypertensive (HT) and 17 normotensive (NT), mildly symptom
atic patients with coronary artery disease (CAD) and ST-segment depression
during exercise were studied before and after seven days of oral enalapril
(EN), which was titrated from 2.5 to 20 mg daily. Patients underwent two tr
eadmill exercise tests and determination of forearm vasodilator response to
BK.
RESULTS Despite receiving a lower dose of EN (7.8 vs. 14.8 mg, p < 0.001),
NT patients had a significant reduction in blood pressure compared to HT pa
tients. Compared to pre-EN, the ischemic threshold, defined as the rate-pre
ssure product at the onset of 1-mm ST depression (p = 0.045), the duration
of exercise to 1-mm ST depression (180 +/- 54 s, p = 0.007) and the maximum
exercise duration (94 +/- 18 s, p < 0.001) were greater after EN in HT pat
ients, but not in NT subjects (all p greater than or equal to 0.3). Patient
s with a greater drop in blood pressure experienced no improvement in exerc
ise-induced ischemia. Forearm blood flow responses to BK were improved with
EN in all patients to a similar extent. Moreover, no correlation was obser
ved between the basal response to BK or the magnitude of its improvement wi
th EN and with either the dose of EN or the improvement in exercise ischemi
c threshold.
CONCLUSIONS Exercise-induced myocardial ischemia is ameliorated in HT patie
nts with CAD by ACE inhibition. (C) 2001 by the American College of Cardiol
ogy.