Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan

Background-Structural and functional alterations of the vasculature may con tribute to complications of hypertension. Because angiotensin II may be piv otal in some of these vascular abnormalities, we tested the hypothesis that the angiotensin type 1 (AT(1)) receptor antagonist losartan, in contrast t o the beta-blocker atenolol, would correct resistance artery abnormalities in patients with essential hypertension. Methods and Results-Nineteen untreated patients with mild essential hyperte nsion (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 r educed 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 diamet er 150 to 350 mu m) dissected from gluteal subcutaneous biopsies were studi ed on a pressurized myograph. After 1 year of treatment, the ratio of the m edia 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 fr om atenolol-treated patients exhibited no significant change (from 8.3+/-0. 3% to 8.8+/-0.5% after treatment). Endothelium-dependent relaxation (acetyl choline-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%). Endotheli um-independent relaxation (by sodium nitroprusside) was unchanged after tre atment. Conclusions-The AT(1) antagonist losartan corrected the altered structure a nd endothelial dysfunction of resistance arteries from patients with essent ial hypertension, whereas the beta-blocker atenolol had no effect.