Angiotensin type 1 receptor antagonism reverses unormal coronary vasomotion in atherosclerosis

OBJECTIVES This study was performed to determine whether angiotensin type 1 (AT1) receptor inhibition improves abnormal coronary vasomotion and endoth elial dysfunction in patients with atherosclerosis or its risk factors. BACKGROUND Endothelial dysfunction, an early feature of atherosclerosis, co ntributes to abnormal vasomotion during stress. Angiotensin II may contribu te to endothelial dysfunction in atherosclerosis. METHODS In 25 patients, mean age 59 +/- 2 years, with atherosclerosis or it s risk factors, we measured coronary vasomotion during flow-mediated dilati on (FMD) in response to adenosine, cold pressor test (CPT) and exercise bef ore and after AT1 receptor blockade with intracoronary losartan (5 mg). RESULTS Losartan did not alter resting coronary vascular tone, but epicardi al FMD improved from 5.6 +/- 1.5% to 8.9 +/- 1.8% (p = 0.02). Abnormal epic ardial 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 co nstriction during stress. Microvascular dilation during adenosine, an endot helium-independent response, was unchanged with losartan. CONCLUSIONS Inhibition of the coronary vascular AT1 receptors in patients w ith atherosclerosis improves epicardial vasomotion during stress, probably by improving endothelial dysfunction. Whether AT1 receptor blockade will pr ovide long-term therapeutic benefits in atherosclerosis needs further inves tigation. (C) 2001 by the American College of Cardiology