2001 Fiscal Year Final Research Report Summary
Role of endothelin-1 in the yenal injury of hypertension
| Project/Area Number |
10670101
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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 |
General pharmacology
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| Research Institution | Osaka University of Pharmaceutical Sciences |
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Principal Investigator |
MATSUMURA Yasuo Osaka University of Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (40140230)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAOKA Masanori Osaka University of Pharmaceutical Sciences Research, 薬学部, 助手 (50140231)
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| Project Period (FY) |
1998 – 1999
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| Keywords | endothelin-1 / hypertension / endothelin type-A receptor / endothelin type-B receptor / renal injury / deoxycorticosterone |
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| Research Abstract |
Among various experimental hypertensive models, we investigated the involvement of endothelin (ET) in the pathogenesis of deoxycorticosterone acetate (DOCA)-salt-induced hypertesion and renal injury in rats. Two weeks after the start of DOCA-salt treatment, the rats were given ABT-627, a selective ET\A receptor antagonist or A-192621, a selective ET_B receptor antagonist for 2 weeks, and their systemic and renal functional parameters were examined. The dily administration of ABT-627 almost completely abolished the development of hypertension and renal dysfunction, and markedly improved the cardiovascular hypertrophy. There were nolesions in glomeruli, tubles and renal small arteries. In contrast, althouth A-192621 did not affect the development of DOCA-salt-induced hypertension, renal dysfunction and tissue injury were deteriorated by this agent. The develpoment of cardiovascular hypertrophy was significantly enhanced by A-192621.These results strongly support the view thet ET_A receptormediated action plays an important role in the pathogenesis of DOCA-salt-induced hypertension. On the other hand, it seems likely that hte ET_B receptor-mediated action protects against vascular and renal injuries, in this model of hypertension
We also found that the contractile responses to noreinephrine were enhanced in mesenteric arteries of DOCA-salt-induced hypertensive rats. This enhancement was declined to the level seen with normotensive animals by ET_B receptor antagonist. Thus, in mesenteric arteries of DOCA-salt-induced hypertensive rats, locally generated ET-1 may contribute to the above enhancement via stimulation of ET_B receptor. In addition, the protein kinase C system seems to be involved in this phenomenon
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Research Products
(12 results)
