Inhibitory effects of a subdepressor dose of L-158,809, an angiotensin II type 1 receptor antagonist, on cardiac hypertrophy and nephropathy via the activated human renin-angiotensin system in double transgenic mice with hypertension.

The effects of L-158,809, an angiotensin II type 1 receptor antagonist, on cardiac hypertrophy and nephropathy were examined using Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. Nine male THM aged 20 weeks were assigned to each of a no-dosage group and an L-158,809 dosage group, and L-158,809 was administered for 8 weeks. Nine age-matched male C57BL/6 mice were used as normal control animals. At 28 weeks of age, all of the mice were euthanized. Systolic blood pressure, urinary volume, water intake volume, urinary albumin excretion, heart weight and kidney weight to body weight ratios and a glomerulosclerosis index were measured. In the no-dosage group, the values of all of these parameters were larger than those in the control mice. In the L-158,809 group, all of the parameters showed significant improvement, except for blood pressure, which was not significantly different from that in the no-dosage group. These results suggest that the renin-angiotensin system played a crucial role in the cardiac hypertrophy and nephropathy in THM, and that L-158,809 exhibited strong curative effects on cardiac hypertrophy and nephropathy by blocking the angiotensin II type 1 receptor.