| Project/Area Number |
10670677
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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 |
Circulatory organs internal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
ARAI Keiko Nippon Medical School, Faculty of Medicine, Assistant Professor, 医学部, 講師 (60277118)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBASAKI Tamotsu Nippon Medical School, Faculty of Medicine, Professor, 医学部, 教授 (00147399)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | amiloride-sensitive sodium channel / hypertension / pseudohypoaldosteronism / polymorphysim / 遺伝子解析 |
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| Research Abstract |
We investigated the role of the amiloride-sensitive sodium channel (ENaC) in the mechanisms underlying the development of hypertension. First, we analyzed the frequency of the polymorphysms of the ENaC in normal subjects, which identified in the patients of the pseudohypoaldosteronism. Pseudohy poaldosteronism is the mirror image of the Liddle syndrome, which is the hereditary hypertension. We found the hamozygous and heterozygous amino acid substitution (Thr^<663>→Ala) of the α subunit of the ENaC (αENaC) gene in 31% and 64% of normal subjects, respectively. This polymorphysm was located at a position close to the C-terminal of the aENaC.The prolin-rich lesion of the C-terminal of the αENaC is important for binding to α-spectrin and for stabilization of the sodium channel in the membrane, suggesting that the above polymorphysm might have functional significance in the salt conservation. Indeed, there is the report that the polymorphysms of the β subunit of the ENaC related to the hypertension of African American and might influence sodium transport. Second, we studied the regulation of the α, βand γsubunits of the ENaC mRNA expression in the kidney of the spontaneous hypertensive rats (SHR-SP(lzm)), which is the one of the model of the salt-sensitive hypertension. The rats revealed hypertension markedly at the age of 16 weeks. The rank order of the expression levels of three subunits of the ENaC mRNA were α>β=γ. The expression levels of all subunits of ENaC of SHR-SP(lzm) rats were lower than those of the control rats. These results suggest that the down regulation of the expression of ENaC in the kidney of the hypertensive rats may have the protective role from the sodium retention and the hypertension.
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