| Project/Area Number |
63570400
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Ehime University |
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Principal Investigator |
MURAKAMI Eiki Ehime University, School of Medicine, Lecturer, 医学部, 講師 (90110832)
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| Co-Investigator(Kenkyū-buntansha) |
SUMIMOTO Takumi Ehime University, Hospital attached to School of Medicine, Associate, 医学部附属病院, 助手 (10187809)
HASHIMOTO Akihide Ehime University, Hospital attached to School of Medicine, ex-Associate (60172855)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1989: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | kidney / renin / mRNA / renin inhibitor / angiotensin converting enzyme inhibitor / 傍糸球体細胞 / ンジオテンシン変換酵素阻害剤 |
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| Research Abstract |
The renin-angiotensin (R-A) system plays an important role in regulating blood pressure and electrolyte balance. We investigated the effects of renin inhibitor, ES-1005 and angiotensin converting enzyme (ACE) inhibitor, captopril on renin gene expression and renin release by the kidney in sodium-depleted marmosets. ES-1005 (bis-[(1-naphthyl)methyl]acetyl-histidyl-statyl-leucil-epsilon-lysinol dihydrochloride) is a specific inhibitor of human and monkey renin with inhibitory constant (Ki) values of 2.4 and 7.9 nM. The relative amount of renin mRNA was measured by densitometric Northern blot analysis using an alpha-^<32>p-labeled human renin cDNA fragment as a hybridization probe. Plasma renin concentration was measured by RIA using a monoclonal antibody to human active renin.
The continuous infusion of ES-1005 (12 mg/kg/h) for 2 hours to marmosets significantly decreased the expression if kidney renin gene. The infusion of captopril (0.53 mg/kg/h, 2 hours) did not affect kidney renin mRNA. ES-1005 (48 mg/kg/day) or captopril (2 mg/kg/day) was administered continuously for 7 days via an osmotic mini-pump. ES-1005-treatment completely inhibited plasma renin activity and significantly decreased the level of kidney renin mRNA (46% of normal control, p<0.01). However, plasma renin concentration was significantly increased by ES-1005 treatment. In contrast, captopril-treatment markedly increased plasma renin activity and kidney mRNA.
The results demonstrated different action on renin synthesis by renin inhibitor and ACE inhibitor. The administration of renin inhibitor, ES-1005 for 7 days showed a paradoxical effect on kidney renin gene expression and renin release by the kidney in sodium-depleted marmosets.
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