CLINICAL STUDIES
Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin-converting enzyme inhibition
A potential role of bradykinin
Abhiram Prasad, MB, MRCPa,
Syed Husain, MDa and
Arshed A. Quyyumi, MD, MRCP, FACCa
a Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA
Manuscript received January 14, 1998;
revised manuscript received October 9, 1998,
accepted November 16, 1998.
Reprint requests and correspondence: Dr. Arshed A. Quyyumi, Cardiology Branch, NHLBI, National Institutes of Health, Bldg. 10, Rm. 7B15, 10 Center Dr. MSC 1650, Bethesda, Maryland 20892-1650
quyyumia{at}gwgate.nhlbi.nih.gov
OBJECTIVES
This study was performed to determine whether angiotensin converting enzyme (ACE) inhibition improves endothelium-dependent flow-mediated vasodilation in patients with atherosclerosis or its risk factors and whether this is mediated by enhanced bradykinin activity.
BACKGROUND
Abnormal coronary vasomotion due to endothelial dysfunction contributes to myocardial ischemia in patients with atherosclerosis, and its reversal may have an antiischemic action. Previous studies have shown that ACE inhibition improves coronary endothelial responses to acetylcholine, but whether this is accompanied by improved responses to shear stress remains unknown.
METHODS
In 19 patients with mild atherosclerosis, metabolic vasodilation was assessed during cardiac pacing. Pacing was repeated during separate intracoronary infusions of low-dose bradykinin (BK) and enalaprilat. Endothelium-dependent and -independent vasodilation was estimated with intracoronary BK and sodium nitroprusside respectively.
RESULTS
Enalaprilat did not alter either resting coronary vascular tone or dilation with sodium nitroprusside, but potentiated BK-mediated dilation. Epicardial segments that constricted abnormally with pacing (–5 ± 1%) dilated (3 ± 2%) with pacing in the presence of enalaprilat (p = 0.002). Similarly, BK at a concentration (62.5 ng/min) that did not alter resting diameter in the constricting segments also improved the abnormal response to a 6 ± 1% dilation (p < 0.001). Cardiac pacing-induced reduction in coronary vascular resistance of 27 ± 4% (p < 0.001) remained unchanged after enalaprilat.
CONCLUSIONS
Thus ACE inhibition: A) selectively improved endothelium-dependent but not -independent dilation, and B) abolished abnormal flow-mediated epicardial vasomotion in patients with endothelial dysfunction, in part, by increasing endogenous BK activity.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | BK | = bradykinin | | NO | = nitric oxide |
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