|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥1,600,000 (Direct Cost : ¥1,600,000)
The distribution of atrial natriuretic peptide (ANP) and pathogenesis of hypertension were examined by immunohistochmistry, electron microscopy and radioimmunoassay in the heart and plasma of Tsukuba hypertensive mouse (R/A) which is transgenic mouse carrying both the human renin gene and the human angiotensinogen gene. The blood pressure of R/A mouse was 30-40mmHg higher than that of control mice (C57BL/6J) at 3 month old and the values tended to be slightly high level with age. The heart weights in R/A mice were significantly larger than that of control mice with age. In R/A mice, the cardiocytes were hypertrophy with age, and the basement membranes of kidney glomerulus were thickening. The numbers and immunoreactivity of ANP-granules in the atrial cardiocytes were significantly increased in comparison with control froups at 3 month old, while these levels were decreased at 12,15,18 month old. The plasma ANP level of R/A mice was about tenfold higher than that of control mice. This level was peak at 7 month old, thereafter was slightly reduced. At 12 month old, plasma ANP level was decreased significantly. ANP levels in atrial and ventricular cardiocytes were significantly higher than that in the control groups. By TEM,in ventricular cardiocytes of R/A mice, ANP-like electrondense granules which were not seen in the control mice were occasionally observed, and the ventricular cardiocytes involving these granules were increased with age. These present study suggests that ANP circulating system and pathogenesis in Tsukuba hypertensive mouse are gratly influenced with age.