Background: We tested the hypothesis that long-term administration of the specific angiotensin II subtype 1 (AT₁)receptor blocker BMS-186295 will regress hypertrophy and modify left ventricular angiotensin converting enzyme (ACE) expression in rats with ascending aortic stenosis. Methods and Results: Six weeks after surgery, rats with ascending aortic stenosis were randomized to receive either the AT₁-receptor blocker BMS-186295 50 mg · kg^-1 · d^{- 1} (n=49), amlodipine 2.5 mg · kg^-1 · d^-1 (n=48) as a positive control for systemic vasodilation, or no drug (n=48) and compared with sham-operated rats (n=39). Drug treatment was continued for 15 weeks. Left ventricular ACE mRNA levels were measured by ribonuclease protection assay. The left ventricular/body weight ratio was increased 43% in hearts from rats with untreated left ventricular hypertrophy (LVH) versus control hearts (P<.05). However, there was no difference in either the left ventricular/body weight ratio (2.78±0.08 versus 2.81±0.20 mg/g; P=NS) or myocyte cross-sectional area in the AT₁-blocker-treated versus untreated LVH hearts. Amlodipine also showed no effect on regression of hypertrophy. In vivo left ventricular systolic pressure was significantly higher in untreated LVH versus sham- operated rats (193±8 versus 118±4 mm Hg; P<.05), and there was a similar severe elevation of left ventricular systolic pressure in the AT₁-blocker- and amlodipine-treated LVH groups (189±9 and 188±16 mmHg; P=NS versus untreated LVH). In vivo left ventricular end-diastolic pressure was higher in the untreated LVH than in the sham-operated rats (14.8±2.3 versus 7.0±0.5 mm Hg; P<.05). Left ventricular end-diastolic pressure was lower in the AT₁- blocker-treated (11.0±1.7 mm Hg) and amlodipine-treated rats (11.5±1.8 mm Hg) and was similar to left ventricular end-diastolic pressure in the sham- operated rats (P=NS). Left ventricular ACE mRNA levels were elevated in untreated LVH rats but were normalized in both the AT₁-blocker-treated rats and amlodipine-treated rats. Conclusions: Long-term AT₁-receptor blockade did not regress LVH in rats with persistent systolic pressure overload due to ascending aortic stenosis. However, both AT₁-receptor blockade and amlodipine improved in vivo left ventricular end-diastolic pressure in association with the normalization of left ventricular ACE mRNA levels.