| Project/Area Number |
12670327
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Saitama Medical School |
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Principal Investigator |
YANAGISAWA Ihroyuki Saitama Medical School, School of Medicin, Assistant professor, 医学部, 助教授 (10200536)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Osamu Saitama Medical School, Schol of Medicine, Profesor, 医学部, 教授 (60009933)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | HgCl_2 / acute renal failure / endothelin / nitric oxide / nitric oxide synthrse / 一酸化窒素分化酵素 |
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| Research Abstract |
The present study was designed to elucidate the mechanisms responsible for the progression of HgC1_2-indnced acute renal failure(ARF). At the glomerulur level, there was endothelin(ET)-1 expression in glomerular mesangial cells, glomlar epithelial cells and juxtaglomernlar cells. However, the expression of endothelial type(e) nitric oxide synthase(NOS) and brain type(b) NOS was observed in glomerular endothelial cells and juxtaglomerular cells and in glomerular epithelial cells and macula densa cells, respectively. ET-1 expression was significantly increased in the HgCl_2-induced ARF model when compared to the control model. Inversely, the expression of eNOS and bNOS was significantly decreased in the HgCl_2-induced ARF model relative to the control model. It is known that ET-1 is a potent vasoconstrictor. Also, it is reported that nitric oxide(NO) derived from eNOS and bNOS is a vasodilator. An increase in ET-1 and a decrease in NO lead to a fall in glomerular filtration rate through a decrement in the ultrafiltration coefficient(Kf) due to glomerular mesangial and epithelial cell contraction and via a decrement in glomerular capillary plasma floW(Q_A) due to an increment in afferent alteriole resistance. Thus, it is suggested that the vasoconstrictor, ET-1 and the vasodilator NO play a crucial role in the progression of HgCl_2-induced ARF through a fall in Kf and Q_A. In addition, prior administration of the angiotensin receptor type 1 antagonist, TCV-116 inhibited ET-1 expression in the HgCl_2-induced ARF model, indicating that angiotensin II may be involved in the regulation of ET-1 expression
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