997-89 Effect of Local Angiotensin II Inhibition on Pattern of Ventricular Hypertrophy and Characteristics of Myocardium

The purpose of this study was to examine the effect of local angiotensin II (ATII) inhibition on amount and pattern of pressure overload-induced ventricular hypertrophy and functional characteristics of myocardium. We administered abdominal aorta-constricted rats vehicle (C), 0.3 mg/kg/day (low dose; LD), and 3.0 mg/kg/day (high dose;HD) of ATII receptor antagonist TCV-116. After 4 weeks treatment, we measured LV pressure using micromanometer and wall thickness using 20 MHz ultrasonic wall tracker for calculating LV dimension (D) and midwall fiber stress (FS). C(n = 7) LD (n = 9) HD(n = 10) Peak LVP (mmHg) 165 ± 10 141 ± 9 * 137 ± 12 * 2.89 ± 003 2.40 ± 0.26 * 2.05 ± 0.20 *# end-diastolic WT (mm) 3.7 ± 0.2 3.0 ± 0.3 * 3.0 ± 0.2 * end-diastolic D(mm) 3.8 ± 0.6 4.6 ± 0.7 * 3.9 ± 0.5 # cell Width ( μ m) 16.3 ± 0.6 1.36 ± 0.3 * 13.4 ± 0.6 * peak FS (×10 3 dyn/cm 2 ) 80 ± 8 86 ± 17 69 ± 8 # k -4.9 -4.9 -8.5 * p l 0.01 vs C, # P l 0.01 vs LD k;the slope of regression line between %shortening of LVD (Y-axis) and peak FS IX-axis) In LD of TCV-116, WT and cell width significantly decreased compared with C in spite of the tendency to increase in peak FS. On the other hand, HD of TCV-116 could inhibit not only development of cell width but also LV dilatation, accompanied with significant reduction of FS. Peak(+)dP/dt of LVP and heart rate did not change between LD and HD. The slope (k) was higher in HO considered as concentric remodeling than in LD as inadequate eccentric remodeling. These results suggest that change in LV geometry and functional characteristics of myocardium could depend on the degree of blocking action of local ATII.