2001 Fiscal Year Final Research Report Summary
Function of vascular endothelium and vasomotor nerve in atherosclerotic animals
| Project/Area Number |
12672213
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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 |
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 |
AYAJIKI Kazuhide Shiga University of Medical Science, Pharmacology, Associate Professor, 医学部, 助教授 (10167968)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMURA Tomio Shiga University qo Medical Science, Pharmacology, Professor, 医学部, 教授 (70152337)
FUJIOKA Hideyuki Shiga University of Medical Science, Pharmacology, Research Associate, 医学部, 助手 (50228970)
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| Project Period (FY) |
2000 – 2001
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| Keywords | lingual, carotid and cerebral arteries / corpus cavernosum / endothelium / nitric oxide (NO) / Ca^<2+>-dependent K^+-channel / cytochrome P450 3A4 / hyperlipidemic rabbit and monkey / atherosclerosis |
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| Research Abstract |
In order to examine the effects of atherosclerosis and hyperlipidemia on vascular function, endothelial function in normal animals was firstly examined (1, 2). Then, the effects of atherosclerosis and hyperlipidemia on the functions of endothelium and vasomotor nerves were examined in Watanabe heritable hyperlipidemic (WHHL) rabbits (3) and hyperlipidemic monkeys fed by a high cholesterol diet (4).
1. In isolated monkey lingual arteries, acetylcholine-induced relaxation was mediated by nitric oxide (NO) and Ca^<2+>-dependent K^<+>-channel opening substarice(s) from arachidonic acid produced by cytochrome P450 3A4 isoform in the endothelium.
2. In isolated dog corpus cavernosum, acetylcholine-induced relaxation was mediated by NO and substance(s) which opens Ca^<2+>-dependent K^<+>-channel of small conductance.
3. Marked, patchy atherosclerotic lesions were observed in all WHHL rabbit carotid arteries. Endothelium-dependent relaxations induced by acetylcholine were significantly inhibited
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in the WHHL rabbit carotid arteries with atherosclerotic lesions. Inversely, endothelium-dependent relaxations by substance P were greater in the arteries with and without atherosclerosis from WHHL rabbits than those in the arteries from Japanese white rabbits. Therefore, atherosclerosis may inhibit the muscarinic receptor function. Long exposure to hyperlipidemia was expected to cause receptor-hypersensitivity of substance P in the endothelium.
4. Atherosclerotic lesions were not observed in middle cerebral arteries (MCA) isolated from hyperlipidemic monkeys fed by a high cholesterol diet. Histamine-induced relaxation, which was mediated by endothelial NO, was significantly potentiated in the hyperlipidemic monkey MCA, compared to that in the arteries from control monkeys whereas the relaxation by Ca^<2+> ionophore A23187 did not differ between control and hyperlipidemic monkeys. Nicotine- induced relaxation in MCA, which was mediated by NO released from nitroxidergic (nitrergic) nerves, was not affected by hyperlipidemia. Therefore, hyperlipidemia did not affect endothelial and nitroxidergic nerve functions of monkey MCA, but enhanced NO-mediated relaxation caused by histamine, possibly due to upregulation of histamine receptor-mediated function in the endothelium.
From the findings using hyperlipidemic rabbits and monkeys, atherosclerosis and hyperlipidemia may modify the specific receptor functions in the endothelium, but not generally affect the functions of endothelium and innervating nerves. Less
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Research Products
(8 results)
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[Publications] Ayajiki, K., Fujioka, H., Toda, N., Okada, S., Minamiyama, Y., Imaoka, S., Funae, Y., Okamura, T.: "EDHF2000, edited by Paul M.Vanhoutte"Taylor & Francis, New York. 502 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Ayajiki K., Fujioka H.,Toda N., Okada S., Minamiyama Y., Imaoka S., Funae Y. and Okamura T.: "An arachidonic acid metabolite(s) produced by the endothelial cytochrome P450 isoform, CYP3A4, relaxes the lingual artery of the monkey via K^+ channel opening"In Vanhoutte P. M. (Eds.), EDHF 2000. Taylor & Francis, New York. 180-186 (2001)
Description
「研究成果報告書概要(欧文)」より
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