| Project/Area Number |
11670709
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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 | TEIKYO UNIVERSITY |
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Principal Investigator |
TAKESHITA Satoshi TEIKYO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (90271288)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | angiogenesis / collaterals / ischemia |
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| Research Abstract |
Background : Impaired microvessel development occurs in spontaneously hypertensive rats (SHR) and in patients with essential hypertension. The purpose of this study was to determine whether collateral development is impaired in SHR, and to what extent it is modified by angiotensin-converting enzyme (ACE) inhibition.
Methods and Results : Ischemia was induced in the hindlimb of SHR by excision of the femoral artery, after which the animals were randomly assigned to receive low-dose perindopril (0.2 mg/kg/day), high-dose perindopril (2.0 mg/kg/day), or vehicle for 3 weeks. Normotensive Wistar-Kyoto rats (WKY) with femoral artery excision served as a control group. Collateral development was significantly impaired at 4 weeks in SHR versus WKY based on a reduced hindlimb perfusion ratio by laser Doppler imaging (0.86 ± 0.08 versus 1.03 ± 0.09, P < 0.05), and a lower capillary density (364.5 + 43.0 versus 463.8 ± 63.0 /mm^2, P < 0.05). Perindopril administration significantly augmented hindlimb perfusion (low dose : 1.06 ± 0.15 ; high dose : 1.05 ± 0.12, P < 0.05 for both) as well as capillary density (low dose : 494.3 ± 69.8 /mm^2 ; high dose : 543.9 ± 76.9 /mm^2, P < 0.005 for both) in SHR. Conclusions : These findings indicate that collateral development is impaired in SHR and that this impairment can be reversed by ACE inhibition. The angiogenic properties of an ACE inhibitor may benefit patients with essential hypertension presenting with lower limb vascular insufficiency.
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