Angiotensin type 1 receptor antagonism reverses abnormal coronary vasomotion in atherosclerosis

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.