The goal of this study was to examine the effect of an angiotensin II type 1 (AT(1))-receptor antagonist (TCV-116) on left ventricular (LV) geometry and function during the development of pressure-overload LV hypertrophy. A low (LD; 0.3 mg.kg(-1). day(-1)) or a high (KD; 3.0 mg.kg(-1).day(-1)) dose of TCV-116 was administered to abdominal aortic-banded rats over 4 wk, and hemodynamics and morphology were then evaluated. In both LD and HD groups, peak LV pressures were decreased to a similar extent compared with the vehicle-treated group but stayed at higher levels than in the sham-operated group. In the LD group, both end-diastolic wall thickness (3.08 +/- 0.14 mm) and myocyte width (13.3 +/- 0.1 mu m) decreased compared with those in the vehicle-treated group (3.67 +/- 0.19 mm and 15.3 +/- 0.1 mu m, respectively; both P < 0.05). In the HD group, myocyte length was further decreased (KD: 82.6 +/- 2.6, LD: 94.1 +/- 2.9 mu m; P < 0.05) in association with a reduction in LV midwall radius (HD: 3.36 +/- 0.12, LD: 3.60 +/- 0.14 mm; P < 0.05) and peak midwall fiber stress (HD: 69 +/- 8, LD: 83 +/- 10 x 10(3) dyn/cm(3); P < 0.05). There was no significant difference in cardiac output among all groups. The BT1-receptor antagonist TCV-116 induced an inhibition of the development of pressure-overload hypertrophy. Morphologically, not-only the width but also the length of myocytes was attenuated with TCV-116, leading to a reduction of midwall radius and hence mall stress, which in turn may contribute to a preservation of cardiac output.
