| Project/Area Number |
03671055
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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 |
Biological pharmacy
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TOKUMURA Akira The University of Tokushima Faculty of Pharmaceutical Sciences Institute for Natural Sources Associate Professor, 薬学部附属医薬資源教育研究センター, 助教授 (00035560)
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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 |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Lysophosphatidic acid / Lysophosphatidylcholine / Lysophospholipase D / Hypertension / Spontaneously hypertensive rat / Plasma phospholipid / Contraction of aorta / 血圧 / 大動脈片 / 血管平滑筋収縮 / リゾホスホリパ-ゼD / 自然発生高血圧ラット |
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| Research Abstract |
Mean arterial blood pressures of spontaneously hypertensive rats(SHR) 5-6 weeks old are significantly higher than those of Wistar Kyoto rats (WKY). Numerous numbers of studies concerning the mechanisms of hyper-tension in SHR have been drawn. In this study,we focussed our interest on a vasopressor phospholipid,lysophosphatidic acid(LPA).
In rat plasma,saturated lysophosphatidylcholines were formed by the action of lecithin-cholesterol acyltransferase during 6-12 hours incubation. The lysophosphatidylcholines were converted into the corresponding LPAs by lysophospholipase D as well as unsaturated lysophosphatidylcholines. The rates of productions of LPAs in SHR were significantly higher than those in WKY. Because the levels of lysophosphatidylcholines in fresh plasma from SHR were almost the same as those from WKY,the activity of lysophospholipase D in SHR plasma was suggested to be higher than that of WKY.
LPA 0.3-10(ug/kg)induced an immediate hypertension and bradycardia both in conscious rats and pentobarbital-anesthetized rats. The pressor responses to LPA of conscious SHR was significantly higher than those of WKY,whereas both SHR and WKY responded to LPA in similar extents.
Next,we examined contractile action of LPA on isolated strips of thoracic aorta of WKY and SHR in Krebs-Henseleit solution or Locke solution. Cumulative addition of LPA induced no contraction of the strips.
At present,the sites of actions of LPA in the circulation remains unclear. Some kinds of vascular smooth muscle cells other than thoracic aorta might be more responsive to LPA than those of WKY. Our results on cardiovascular effects of LPA together with the finding that LPA accumulated more rapidly in SHR plasma than in WKY plasma,indicated that this physiologically active phospholipid is involved in an early phase of hypertension in SHR.
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