1994 Fiscal Year Final Research Report Summary
Relationship between PKC dependent smooth muscle contraction and lipid peroxidation in the pathogenesis of cerebral vasospasm after SAH
| Project/Area Number |
05671167
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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 |
Cerebral neurosurgery
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| Research Institution | Ehime University School of Medicine |
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Principal Investigator |
SASAKI Saburo Department of Neurological Surgery, Ehime University School of Medicine.Professor, 医学部, 教授 (30116933)
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| Co-Investigator(Kenkyū-buntansha) |
KOHNO Kanehisa Department of Neurological Surgery, Ehime University school of Medicine.Associat, 医学部・附属病院, 講師 (60145076)
OHTA Shinsuke Department of Neurological Surgery, Ehime University School of Medicine.Associat, 医学部・附属病院, 講師 (50194163)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Cerebral Vasospasm / Protein Kinase C / Lipid Peroxidation / Diacylglycerole / Subarachnoid Hemorrhage |
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| Research Abstract |
The mechanism of the induction of protein kinase C (PKC) -dependent vascular contraction independent of the increase of intracellular Ca^<++> was investigated in the pathogenesis of cerebral vasospasm in the double subarachnoid hemorrhage (SAH) model dogs. The level of 1,2-diacylglycerol (DAG) , which is an intrinsic PKC activator, significantly increased from days 4 to 7 in the basilar artery after the initial SAH,and the continuous administration of 1,2-bis (nicotinamido) -propane (AVS) , a novel free radical scavenger, not only lowered the concentration of lipid peroxides in cerebrospinal fluid but also cuccessfully suppressed the basilar arterial narrowing and the increase of DAG in the basilar arterial wall in the same model. It was suggested that lipid peroxides generated in the subarachnoid clot affect the DAG content of the cerebral artery. Analysis of hydroxyeicosatetraenoic acids (HETEs) with high performance liquid chromatography (HPLC) revealed the production of relatively large amount of 12-HETE in the subarachnoid clot. To examine the potential effect of exogenous 12-HETE on the DAG content of the cerebral artery, the basilar artery was incubated with 12-HETE in vitro. 12-HETE induced a concentration-dependent slow increase in DAG content in the basilar arterial wall after 6 hours of the incubation. Under conditions in which DAG formation was facilitated by the Ca^<++>-ionophore, DAG accumulation in the basilar artery was enhanced in the presence of 12-HETE.It was suggested that 12-HETE generated in the subarachnoid clot induced DAG formation in the arterial wall by inhibition of DAG metabolism, resulting in the induction of prolonged PKC-dependent smooth muscle contraction in the pathogenesis of cerebral vasospasm.
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