Reversal of vascular hypertrophy in hypertensive patients through blockade of angiotensin II receptors.
Angiotensin II (Ang II) has been linked to vascular dysfunction and target-organ damage. Blockade of the angiotensin II type 1 receptor (AT(1)) with an angiotensin receptor blocker may reverse vascular pathology independent of blood pressure (BP) lowering. Stage I hypertensive, nondiabetic patients (61% male; age 38 to 67 years) were randomized after a 4-week washout period to olmesartan medoxomil 20 to 40 mg or atenolol 50 to 100 mg plus additional agents (hydrochlorothiazide, amlodipine, or hydralazine) as needed for a goal BP <140/90 mm Hg. At baseline and after 1 year of treatment, subcutaneous gluteal resistance arteries were examined on a pressurized myograph to evaluate remodeling. Biopsies were available from 22 atenolol recipients, 27 olmesartan medoxomil recipients, and 11 normal volunteer controls. BP was reduced to a comparable degree by olmesartan medoxomil (from 149 +/- 11/92 +/- 8 mm Hg to 120 +/- 9/77 +/- 6 mm Hg; P < .05 [mean +/- standard deviation]) and atenolol (from 147 +/- 10/90 +/- 6 mm Hg to 125 +/- 12/78 +/- 7 mm Hg; P < .05 [mean +/- standard deviation]) from baseline for each arm (P = .08 for the 40-week treatment mean between arms). After one year's treatment, the wall-to-lumen ratio in arteries from patients treated with olmesartan medoxomil was significantly reduced (from 14.9% to 11.1%; P < .01), whereas no significant change was observed in arteries from atenolol-treated patients (from 16.0% to 15.5%; P = NS); the wall-to-lumen ratio in controls was 11.0%. Blockade of AT(1) receptors showed a superior corrective effect on the altered structure of resistance arteries in essential hypertension that was independent of the magnitude of BP reduction, and resulted in values similar to those in normotensive controls.
Smith
Ronald D
RD
Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Yokoyama
Hiroshi
H
Averill
David B
DB
Schiffrin
Ernesto L
EL
Ferrario
Carlos M
CM