| Project/Area Number |
62570384
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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 | University of Tokyo (1988)
Dokkyo Medical University (1987) |
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Principal Investigator |
UEHARA Yoshio University of Tokyo, 医学部(病), 助手 (40184965)
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| Co-Investigator(Kenkyū-buntansha) |
YAGI Shigeru Dokkyo University School of Medicine, 医学部(病), 教授 (90049130)
MATSUOKA Hiroaki University of Tokyo, 医学部(病), 講師 (20111544)
ISHIMITSU Toshihiko University of Tokyo (80232346)
ISHII Masao Yokohama City University (90010363)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1987: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Thromboxane inhibitory factor / Salt-induced hypertension / Prostaglandins / Phospholipase C / Phospholipase A2 / Vascular smooth muscle cells / Cell growth / 血管中膜過形成 / プロスタグランジン / フォスフォリパーゼC / フォスフォリパーゼA_2 / プロスタグランジン産生阻害因子 / Dahl食塩感受性ラット高血圧自然発症ラット / l腎性腎血管性高血圧ラット / DOCA食塩高血圧ラット / フォスフォリパーゼ |
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| Research Abstract |
In this study we determined a plasma factor(s), which inhibits platelet thromboxanes generation, in genetic (Dahl salt sensitive rats) and secondary hypertensive (DOCA-salt and one kidney Goldblatt hypertensive rats) model both of which are closely related to volume hypertension. This plasma factor was able to inhibit vasodepressor PGE_2 production in platelet and lowered renal prostablandins biosynthesis as well. The molecular weight was estimated to be around 4300 dalton. the factor had a peptide like moiety in its chemical structure. The inhibitory mechanisms were largely attributable to the inhibition of phospholipase C and A_2 and the subsequent reduction of free arachidonic acid. Indeed, PLC-inhibitory activity occurred in the circulating plasma of volume-dependent hypertensive rats. Moreover, such hypertensive rats exhibited a decrease of PLC activity in the arterial walls when compared to the respective normotensive controls. Thus, it is indicated that prostaglandin inhibitory factor is characteristically observed in volume-dependent hypertensive rats and that it is possibly related to a decrease of vascular prostaglandins generation in volume-dependent hypertensive rats models. We demonstrated as well that vasodepressor prostaglandins retard vascular smooth muscle cells growth. The altered prostaglandins metabolism observed in volume-dependent hypertension is likely to contribute to a medial hyperplasia of the arterial walls, an integral component of arterial sclerotic changes. It seems of great use to explore where the factor is produced and how the action of the factor could be inhibited. Further experiments are required.
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