(Circulation. 2000;101:1653.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Correction of Arterial Structure and Endothelial Dysfunction in Human Essential Hypertension by the Angiotensin Receptor Antagonist Losartan
From the Medical Research Council Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada.
Background—Structural and functional alterations of the vasculature may contribute to complications of hypertension. Because angiotensin II may be pivotal in some of these vascular abnormalities, we tested the hypothesis that the angiotensin type 1 (AT1) receptor antagonist losartan, in contrast to the ß-blocker atenolol, would correct resistance artery abnormalities in patients with essential hypertension.
Methods and Results—Nineteen untreated patients with mild essential hypertension (47±2 years, range 30 to 65 years; 57% male) were randomly assigned in double-blind fashion to losartan or atenolol treatment for 1 year. Nine age/sex-matched normotensive subjects were also studied. Both treatments reduced blood pressure to a comparable degree (losartan, from 149±4.1/101±1.6 to 128±3.6/86±2.2 mm Hg, P<0.01; atenolol, from 150±4.0/99±1.2 to 130±3.2/84±1.4 mm Hg, P<0.01). Resistance arteries (luminal diameter 150 to 350 µm) dissected from gluteal subcutaneous biopsies were studied on a pressurized myograph. After 1 year of treatment, the ratio of the media width to lumen diameter of arteries from losartan-treated patients was significantly reduced (from 8.4±0.4% to 6.7±0.3%, P<0.01). Arteries from atenolol-treated patients exhibited no significant change (from 8.3±0.3% to 8.8±0.5% after treatment). Endothelium-dependent relaxation (acetylcholine-induced) was normalized by losartan (from 82.1±4.9% to 94.7±1.1%, P<0.01) but not by atenolol (from 80.4±2.7% to 81.7±4.6%). Endothelium-independent relaxation (by sodium nitroprusside) was unchanged after treatment.
Conclusions—The AT1 antagonist losartan corrected the altered structure and endothelial dysfunction of resistance arteries from patients with essential hypertension, whereas the ß-blocker atenolol had no effect.
Key Words: arteries • blood pressure • endothelium • hypertrophy • receptors • remodeling
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