Role of the renin-angiotensin system in cardiac hypertrophy and renal glomerular sclerosis in transgenic hypertensive mice carrying both human renin and angiotensinogen genes

Tsukuba hypertensive mice (THMs) are transgenic mice carrying human renin and angiotensinogen genes. The aim of this study was to evaluate the role of the renin-angiotensin system (RAS) in cardiac hypertrophy and renal disorders in THMs. After a 2-wk control period, 10-wk-old THMs were treated with lisinopril (ACEI group) or hydralazine (hydralazine group) or left untreated (control group) for 8 wk. C57BL/6 mice of similar age (wild group) were used as normal controls. systolic blood pressure and urinary albumin excretion were measured once a week. All mice were sacrificed at 20 wk of age, and heart to body weight ratio, cardiac myocyte diameter, renal glomerular sclerosis index, and glomerular size were measured. Fibronectin expression was also evaluated, At 20 wk of age, systolic blood pressure and urinary albumin excretion in the control group were significantly higher than those in the wild group and significantly lower than those in the ACEI and hydralazine groups, Heart to body weight ratio and cardiac myocyte diameter were significantly higher in the hydralazine and control groups than in the other groups. Renal glomerular sclerosis index and glomerular size were also significantly higher in the control group than in the other groups, and there were significant differences between the ACEI and hydralazine groups in these variables. Fibronectin expression was marked in the control and hydralazine groups. These findings suggest that the RAS plays an important role in cardiac hypertrophy in THMs, but that both the RAS and elevation of blood pressure contribute to the pathogenesis of renal glomerular sclerosis.