Molecular-Pharmacological Analysis of Periodontal Disease : Interaction between LPS and Kinins on Microcirculation of Oral Region

在本研究项目中，我们希望确定1）缓激肽对舌动脉的作用; 2）LPS和缓激肽对舌动脉的相互作用; 3）LPS对透壁神经刺激诱导的离体肠系膜动脉收缩的作用。研究了氧自由基参与LPS的作用。获得了以下结果：1.缓激肽引起的收缩可能是通过B_2受体偶联的磷脂酰肌醇（PI）更新引起的细胞内游离Ca ~（2+）增加而介导的;缓激肽引起的舒张可能是通过内皮细胞B_2受体激活鸟苷酸环化酶，释放血管舒张物质（如一氧化氮）而介导的。2.内毒素诱导家兔B_1-激肽受体的形成。去精氨酸缓激肽激活B_1-激肽受体可引起兔舌动脉收缩 ...更多信息 3.LPS通过刺激连接前抑制性M受体和α_2受体抑制交感神经末梢释放去甲肾上腺素。LPS的作用可能与蛋白质合成有关。4. LPS本身可以通过超氧化物依赖性和/或芬顿和哈伯-韦斯反应产生氧自由基（OH自由基）。5. OH自由基选择性损伤内皮依赖性舒张。它也被假定，脂质过氧化可能是负责这种effect.Finally，它是可能的，一个顺序激活或/和缓激肽，激肽类似物，胰高血糖素，和氧自由基通过LPS相互作用的调节活性参与牙周病的进展。此外，现在必须开始将LPS对血管反应性的作用的功能性受体从头形成假说放在正确的角度。深入了解口腔组织中血液动力学的内源性调节机制，可能对未来牙科治疗学新概念的发展感兴趣。少

In this research project, we wished to determine 1) the effect of bradykinin on lingual artery ; 2) the interaction between LPS and bradykinin on lingual artery and 3) the effect of LPS on transmural nerve stimulation-induced contraction of the isolated mesenteric artery. Oxygen free radical participation in the effect of LPS was investigated. The following results were obtained : 1. Bradykinin-induced contraction may be mediated by an increase of intracellular free Ca ion by B_2 receptors-coupled phosphoinositide (PI) turnover in canine vascular smooth muscle, and bradykinin-induced relaxation may be mediated by a liberated vasodilator substance (e.g.nitric oxide) by the stimulation of the endothelial B_2 receptors, which possibly activates guanylate cyclase to accumulate cGMP in smooth muscle. 2. LPS induces the formation of B_1-kinin receptor in rabbits. The activation of B_1-kinin receptors by des-Arg^9-bradykinin produces contraction of the lingual arteries isolated from the rabbi … More t intravenously treated with LPS.3.LPS inhibits the release of norepinephrine from sympathetic nerve endings by stimulating both prejunctional inhibitory muscarinic- and alpha_2-adrenoceptors. The effect of LPS may involved protein synthesis. 4. LPS by itself can generate oxygen free radicals ( OH radical) via superoxide-dependent and/or Fenton and Harber-Weiss reactions. 5. OH radical selectively damage endothelium-dependent relaxation. It is also postulated that lipid peroxidation may be responsible for this effect.Finally, it is likely that a sequential activation or/and a modulatory activity of bradykinin, kinin analogous, prostaglandins, and oxygen free radicals via the LPS-interaction is involved in the progression of periodontal disease. Furthermore, one must now begin to put the functional receptor de novo formation hypothesis of the effect of LPS on vascular reactivity in perspective. A through understanding of the endogenous regulatory mechanisms of hemodynamics in oral tissues may be of interest for the development of new concepts of treatment in dental therapeutics in the future. Less