| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
The angiotensinogen (ATN) is an important determinant for both blood pressure and electrolyte homeostasis. We have already shown that intravenous injection of antisense oligodeoxynucleotides (ODNs) against rat ATN coupled to asialoglycoprotein carrier molecules significantly decreased both the plasma ATN and angiotensin II (Ang. II) contents as well as systolic blood pressure (BP) in spontaneously hypertensive rats (SHR). The present study was therefore examined whether the chronic treatment with this antisense ODNs can affect the cardiac remodeling process in SHRs. The antisense ODNs was intravenously injected to 10-weeks -old SHRs for 10 weeks via their tail veins (A-SHR, n=12) which were compared with SHRs injected with the sense ODNs (S-SHR, n=9) and the untreated SHR (U-SHR, n=9). At the end of those treatment, the both ATN and Ang II concentrations in plasma significantly (p<0.01) decreased in A-SHR (-38%, -58%, respectively) compared with those of S-SHR or U-SHR. The BP in A-SHR
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(168±5.4 mmHg) was significantly reduced (p<0.05) in comparison with those of S-SHR (202±8.4) or SHR (198±7.6), although BP in A-SHR were still higher than that in Wistar Kyoto rats (148±5.3) (p<0.05). The both of the left ventricular (LV) weight and the ratio of LV to body weight also significantly reduced in A-SHR (952±21.2mg, 26.5±0.071mg/g, respectively) compared with S-SHR (1079±32.4, 2.85±0.079) or SHR (1068±39, 2.90±0.080). The Northern blotting showed that the hepatic mRNA expressions for ATN were reduced only in A-SHR, but not in S-SHR or U-SHR. There were no difference in the levels of LV collagen concentration among each SHR group. The mRNA expressions for angiotensin II type 1 receptor (AT1) were more enhanced in LV of A-SHR, but there were no difference in those of angiotensin converting enzyme and type II receptor (AT2) among each SHRs group. These results indicate that the suppression of ATN mRNA can alter the remodeling process in hypertrophy of SHR despite of the partial BP and suggest that the plasma ATN plays a crucial role in the myocyte hypertrophy of LV in SHR, but not in the collagen accumulation of the interstitum. Less
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