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

OBJECTIVES We investigated whether augmentation of bradykinin (BK) bioavailability with angiotensin-converting enzyme (ACE) inhibition is associated with reduced exercise-induced myocardial ischemia in hypertension. BACKGROUND Bradykinin responses are depressed in hypertension, and endothelial dysfunction contributes to myocardial ischemia by promoting abnormal coronary vasomotion during stress. METHODS Fourteen hypertensive (HT) and 17 normotensive (NT), mildly symptomatic 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 treadmill 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 patients. Compared to pre-EN, the ischemic threshold, defined as the rate-pressure 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 patients, but not in NT subjects (all p ≥ 0.3). Patients with a greater drop in blood pressure experienced no improvement in exercise-induced ischemia. Forearm blood flow responses to BK were improved with EN in all patients to a similar extent. Moreover, no correlation was observed between the basal response to BK or the magnitude of its improvement with EN and with either the dose of EN or the improvement in exercise ischemic threshold. CONCLUSIONS Exercise-induced myocardial ischemia is ameliorated in HT patients with CAD by ACE inhibition.