CLINICAL STUDY
Angiotensin type 1 receptor antagonism reverses abnormal coronary vasomotion in atherosclerosis
Abhiram Prasad, MD, MRCP*,
Julian P. J. Halcox, MA, MRCP*,
Myron A. Waclawiw, PhD and
Arshed A. Quyyumi, MD, FRCP, FACC*
* Cardiology Branch, Bethesda, Maryland, USA
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA
Manuscript received September 29, 2000;
revised manuscript received June 6, 2001,
accepted June 26, 2001.
Reprint requests and correspondence: Dr. Arshed A. Quyyumi, National Institutes of Health, Cardiology Branch, NHLBI, Building 10, Room 7B15, 10 Center Drive, MSC 1650, Bethesda, Maryland 20892-1650
quyyumia{at}nih.gov
OBJECTIVES
This study was performed to determine whether angiotensin type 1 (AT1) receptor inhibition improves abnormal coronary vasomotion and endothelial dysfunction in patients with atherosclerosis or its risk factors.
BACKGROUND
Endothelial dysfunction, an early feature of atherosclerosis, contributes to abnormal vasomotion during stress. Angiotensin II may contribute to endothelial dysfunction in atherosclerosis.
METHODS
In 25 patients, mean age 59 ± 2 years, with atherosclerosis or its risk factors, we measured coronary vasomotion during flow-mediated dilation (FMD) in response to adenosine, cold pressor test (CPT) and exercise before and after AT1 receptor blockade with intracoronary losartan (5 mg).
RESULTS
Losartan did not alter resting coronary vascular tone, but epicardial FMD improved from 5.6 ± 1.5% to 8.9 ± 1.8% (p = 0.02). Abnormal epicardial vasomotion during CPT and exercise also improved with losartan from –1.7 ± 0.8% to 1.5 ± 0.1% (p = 0.02) and –0.6 ± 0.9% to 3.4 ± 1.2% (p = 0.009), respectively. Improvement in epicardial vasomotion was most prominent in segments with baseline endothelial dysfunction evidenced as constriction during stress. Microvascular dilation during adenosine, an endothelium-independent response, was unchanged with losartan.
CONCLUSIONS
Inhibition of the coronary vascular AT1 receptors in patients with atherosclerosis improves epicardial vasomotion during stress, probably by improving endothelial dysfunction. Whether AT1 receptor blockade will provide long-term therapeutic benefits in atherosclerosis needs further investigation.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme activity | | AT1 | = angiotensin type 1 | | AII | = angiotensin II | | CPT | = cold pressor test | | FMD | = flow-mediated dilation | | NADH/NADPH | = nicotinamide adenine dehydrogenase/nicotinamide adenine phosphate dehydrogenase | | NO | = nitric oxide |
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