| Project/Area Number |
03807153
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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 |
応用薬理学・医療系薬学
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| Research Institution | SHIGA UNIVERSITY OF MEDICAL SCIENCE |
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Principal Investigator |
OKAMURA Tomio Shiga University of Medical Science Department of Pharmacology, Associate Professor, 医学部, 助教授 (70152337)
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| Co-Investigator(Kenkyū-buntansha) |
AYAJIKI Kazuhide Shiga University of Medical Science Department of Pharmacology, Instructor, 医学部, 助手 (10167968)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Renin / Angiotensin / Angiotensin-converting enzyme / Renin antibody / Immunohistochemistry / Vascular endothelium / Renin inhibitor / Human artery / ヒト血管 / 血管壁 / 腎摘ラット |
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| Research Abstract |
Recently, effectiveness of angiotensin-converting enzyme (ACE) inhibitors has been clinically validated and regarded as one of the first-line drugs for the treatment of hypertension. Mechanisms of action of ACE inhibitors have not solely been explained by inhibition of circulating renin-angiotensin system or potentiation of kallikrein-kinin system. We found that elevation of vascular ACE activity is closely related to the development and maintenance of chronic renal hypertension. Thereafter, the physiological and pathophysiological importance of vascular renin-angiotensin system has been recognized, but mechanism of angiotensin I generation in the vascular tissues remained unknown. In the present study, firstly, possible existence of vascular renin was biochemically demonstrated by measuring alterations in plasma and vascular renin activity (angiotensin I generating activity sensitive to antirenin antibody) in bilaterally nephrectomized rats. Vascular renin activity was detected also i
… More
n human gastroepiploic arteries under non-pathological conditions. Further, renin activity in human arteries with endothelium was significantly higher than in those without endothelium, suggesting the existence of renin in the vascular endothelium. Secondly, vascular renin was immunohistochemically stained using a modified avidine-biotin-peroxidase complex method with anti-human recombinant renin antibody; positive staining selectively occurred in the endothelial cells. These results suggest that renin is present in endothelial cells of arteries under physiological conditions. Whether renin is taken up by the endothelial cells or synthesized in the cells could not be determined. However, in any event, We concluded a possible generation of angiotensin I in the vascular endothelium. It has been suggested that vascualar endothelium plays an important role in the initiation, development and maintenance of hypertension and atherosclerosis. The present study on the vascular renin -angiotensin system emphasizes the importance of endothelial function in the regulation of vascular tone and smooth muscle cell proliferation. Less
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