| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Human chymase produces a novel endothelin-1 with 31 amino-acid length ET-1 (1-31), which is longer than conventional ET-1, ET-1 (1-21). The aim of our study was to investigate the role of ET-1 (1-31) on porcine coronary vascular smooth muscle cell (VSMC). BQ485, an ETA receptor antagonist, completely abolished ET-1 (1-31)-induced contraction, but BQ788, an ETB receptor antagonist, slightly enhanced it, suggesting that ET-1 (1-31) relaxes artery via endothelium. On endothelial cells, ET-1 (1-21) and ET-1 (1-31) increased [Ca2+]i and produced NO, both of which were significantly inhibited by BQ788 and not by BQ485. These results indicate that ET-1 (1-31) increased [Ca2+]i and produced NO in endothelial cells through ETB receptor similarly with ET-1 (1-21). Although the increase in [Ca(2+)](i) by ET-1 (1-31) and contraction of artery was 10 times weaker than that of ET-1 (1-21), ET-1 (1-31) showed equivalent potency in VSMC proliferation, c-fos/c-myc mRNA expression and cell cycle analysis with ET-1 (1-21). ET-1 (1-31) significantly induced expression of cyclin D1 but not those of cyclin D2 or D3. These effects were specifically inhibited by BQ485. These results indicate that ET-1 (1-31) also can involve a VSMC proliferation process such as atherosclerosis.
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