Mode of Action of Endogenous Vasoactive Substances on Blood Vessels in Oral Region : Its Molecular Pharmacological Analysis

内源性血管活性物质对口腔血管的作用方式：分子药理学分析

• 批准号: 04404073
• 负责人: ITO Haruo
• 金额: $ 14.4万
• 依托单位: Kanagawa Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04404073/
• 关键词: 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

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.

本研究旨在探讨脂多糖（lipopolysaccharide，LPS）等血管活性物质与氧自由基之间的相互作用对舌动脉血管反应性的影响，以及氧自由基对血管平滑肌细胞内Ca^2+转导的影响，并确定3）氧衍生自由基对血管收缩-舒张周期的影响。缓激肽通过B_2-激肽受体操纵的Ca ^<2+>通道和Na^+-Ca^<2 +>交换机制刺激Ca^<2 +>内流，使犬舌动脉环产生非内皮依赖性收缩。氧自由基使B_2-激肽受体对激肽敏感。此外，LPS增加连接前α_2-和毒蕈碱受体的敏感性，氧自由基产生的LPS本身。因此推测，一旦氧自由基产生，牙周膜血管网的功能就会受到干扰.氧自由基抑制兔舌动脉环平滑肌细胞肌浆网Ca^2+释放，并通过电压依赖性Ca^2+通道促进Ca^2+内流.降钙素基因相关肽（CGRP）作为扩血管物质存在于犬舌动脉血管周围神经中。经体外自由基产生系统（H_2O_2 + FeSO_4）处理后，CGRP样免疫反应性明显减弱，内毒素LPS能产生氧自由基，直接刺激骨吸收，提示LPS介导的氧自由基的产生可导致牙周组织循环衰竭。

项目成果

Kazu-ichi Yoshida: "Selective Impairment of Endothelium-Dependent Relaxation by Sevoflurane: Oxygen Free Radicals Participation" Anesthesiology. 76. 440-447 (1992)

Kazu-ichi Yoshida：“七氟烷对内皮依赖性松弛的选择性损伤：氧自由基参与”麻醉学。

岡部栄逸朗: "フリーラジカルと心筋酸化ストレス" 現代医療. 25. 3371-3379 (1993)

Eiichiro Okabe：“自由基和心肌氧化应激”现代医学 25. 3371-3379 (1993)。

Okabe E: "Singlet oxygen and ischemia-reperfusion injury in isolated perfused rat hearts." Stract.Metabolism Heart. 16. 49-55 (1994)

Okabe E：“离体灌注大鼠心脏中的单线态氧和缺血再灌注损伤。”

Okabe E: "A mechanism underlying free radical-induced increase in release of Ca through Ca-release channels of cardiac sarcoplamic reticulum." Struct.Matabolism Heart. 16. 57-62 (1994)

Okabe E：“自由基通过心脏肌浆网钙释放通道诱导钙释放增加的机制。”

Lee M: "A mechanism underlying free radical-mediated reduction of Ca, Mg-ATPase activity of skeletal muscle sarcoplasmic reticulum." Magnetic Resonance. 16 (in press.). (1994)

Lee M：“自由基介导的骨骼肌肌浆网 Ca、Mg-ATP 酶活性降低的机制。”