Anti-ischemic effects of angiotensin-converting enzyme inhibition in hypertension

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.