| Project/Area Number |
04404073
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional basic dentistry
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| Research Institution | Kanagawa Dental College |
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Principal Investigator |
ITO Haruo Kanagawa Dental College, Pharmacology, Professor, 歯学部, 教授 (10084716)
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| Co-Investigator(Kenkyū-buntansha) |
LEE Masaichi Kanagawa Dental College, Pharmacology, Instructor, 歯学部, 助手 (60220795)
TAKAHASHI Shun-suke Kanagawa Dental College, Pharmacology, Instructor, 歯学部, 助手 (60206810)
TODOKI Kazuo Kanagawa Dental College, Pharmacology, Assistant Professor, 歯学部, 講師 (90139577)
OKABE Eiichiro Kanagawa Dental College, Pharmacology, Associate Professor, 歯学部, 助教授 (50097276)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥22,500,000 (Direct Cost: ¥22,500,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥13,500,000 (Direct Cost: ¥13,500,000)
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| Keywords | Vasoactive substances / Endothelial cells / Free radicals / Periodontitis / Lipopolysaccharides / エンドトキシン / カルシトニン遺伝子関連ペプチド / 口腔内血管 |
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| Research Abstract |
In this research project, we wished to investigate 1) interaction between vasoactive substances include lipopolysaccharide (LPS) and oxygen-derived free radicals on the vascular reactivity in lingual artery, to characterize 2) intracellular Ca^<2+> transduction of the vascular smooth muscle in relation to oxygen-derived free radicals, and to define 3) the effect of oxygen-derived free radicals on the vascular contraction-relaxation cycle.
1. Bradykinin produces endothelium-independent contraction of canine lingual artery ring preparations via stimulation of Ca^<2+> influx through B_2-kinin recaptor-operated Ca^<2+> channel and Na^+-Ca^<2+> exchange mechanism. Oxygen free radicals sensitize B_2-kinin receptors to kinins. Further, LPS increases prejunctional alpha_2- and muscarinic receptor sensitivity ; oxygen free radicals were produced from LPS itself. Therefore, it is hypothesized that once oxygen free radicals produced function of periodontal vascular network could be disturbed.
2. Oxygen-derived free radicals produced inhibition of Ca^<2+> release from sarcoplasmic reticulum of vascular smooth muscle cells and stimulation of Ca^<2+> influx through voltage-dependent Ca^<2+> channel in rabbit lingual artery ring preparations in vitro.
3. Calcitonin gene-related peptide (CGRP) was found to exist as the vasodilator substance in perivascular nerves in the canine lingual artery. The CGRP-like immunoreactivity was markedly diminished after treatment with in vitro free radical generating system (H_2O_2 plus FeSO_4).
Endotoxin LPS may directly stimulate bone resorption due to its ability to generate oxygen free radicals ; therefore, the results stated above postulate that LPS-mediated generation of oxygen free radicals may produce circulatory failure in periodontal tissues.
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