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Phathophysiology of Circulatory Failure in Oral Region : Its Pharmacological Analysis

口腔循环衰竭的病理生理学:药理学分析

基本信息

批准号：
01480438
负责人：
ITO Haruo
金额：
$ 3.97万
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 (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

In this research project, we wished to determine the effect of LPS on 1)arterial microvascular dimensions in hamster cheek pouch ; 2)dilatory response of isolated carotid artery of hamster ; 3)the responses of isolated lingual artery of rabbit to kinins B_1-receptor agonist ; and 4)transmural nerve stimulation-induced contraction of the isolated rabbit mesenteric artery and vein. Oxygen free radical participation in the effect of LPS was also determined.1. The effect of LPS(E Coli, Difco)on arterial microvascular dimensions was studied in hamster cheek pouch. The data, coupled with other observations, support the hypothesis that loss of tone and loss of contractile activity in the arteriole induced by LPS produce an increase in diameter of terminal arteriole, thereby causing an increase in blood flow through terminal arteriole to the venule.2. The role of endothelial cells in the dilatory response of carotid artery to LPS was studied in vitro using perfused arterial segments of hamster … More . The results obtained in this series of study support the concept that LPS can induce the release of dilating substance(s)from endothelial cells through the lipoxygenase pathway of arachidonic acid metabolism.3. The effect of intravenous injection of 10 mug of LPS extracted from E. coli to rabbits on the responses of isolated lingual arteries to des-Arg^9-bradykinin(a specific kinins B_l-receptor agonist)was studied. From the results of this study, we propose that systemic administration of LPS induces the formation of kinin B_l-receptors via some cycloheximide or actinomycin D-sensitive steps of protein synthesis in rabbits, and that the activation of kinin B_l-receptors by des-Arg^9-bradykinin produces contraction of the lingual arteries isolated from the animals treated with LPS.4. Systemic administration of LPS produces a potent blocking action on vascular alpha-adrenoceptors. To assess further the effect of LPS, we measured the changes in isometric tension of isolated rings of rabbit mesenteric arteries induced by electrical nerve stimulation. It can be concluded from the obtained data that treatment of rabbits with LPS appears to be able to inhibit the release of endogenous norepinephrine from sympathetic nerve endings by stimulating both prejunctional inhibitory muscarinic receptors and alpha_2-adrenoceptors.5. The effect of in vitro exposure of sarcolemmal membrane(SL)vesicles to LPS was studied. The observed findings in this experiment suggest that LPS damages cardiac SL by an oxygen free radical mechanism by the generation of 'OH, due to inhibition of Na, K-ATPase activity and peroxidation of lipids, and that the effect of LPS is not dependent on the presence of contaminating iron.Finally, one must now begin to put the oxygen free radical hypothesis of the effect of LPS on vascular reactivity in perspective. It remains an open area of investigation. Less

本研究旨在观察脂多糖（LPS）对金黄地鼠颊囊动脉微血管的影响，对金黄地鼠颈动脉的舒张反应，对家兔舌动脉对激肽B_1受体激动剂的反应，以及对家兔肠系膜动、静脉跨壁神经刺激收缩的影响。氧自由基参与LPS的作用.本文研究了脂多糖（LPS）对金黄地鼠颊囊动脉微血管的影响。这些数据，结合其他观察结果，支持这样的假设，即由LPS引起的小动脉张力的丧失和收缩活动的丧失导致终末小动脉直径的增加，从而导致通过终末小动脉到微静脉的血流量增加.采用离体灌流的金黄地鼠颈动脉，研究内皮细胞在脂多糖（LPS）扩张颈动脉反应中的作用 ...更多信息 .本系列研究结果支持了LPS通过花生四烯酸代谢的脂氧合酶途径诱导内皮细胞释放扩张物质的观点.静脉注射10 μ g E.大肠杆菌感染兔舌动脉后，对特异性激肽B_1受体激动剂去精氨酸缓激肽（des-Arg^9-bradykinin）作用的影响。根据本研究的结果，我们认为全身给予LPS通过放线菌酮或放线菌素D敏感的蛋白质合成步骤诱导了激肽B_l受体的形成，并且通过去精氨酸缓激肽激活激肽B_l受体引起了从LPS处理的动物中分离的舌动脉的收缩。LPS的全身给药对血管α-肾上腺素受体产生有效的阻断作用。为了进一步评价LPS的作用，我们测量了电刺激神经引起的离体兔肠系膜动脉环等长张力的变化。从所获得的数据可以得出结论，用LPS处理家兔似乎能够通过刺激连接前抑制性M受体和α_2-肾上腺素受体来抑制交感神经末梢释放内源性去甲肾上腺素。本文研究了体外暴露于脂多糖（LPS）对肌膜囊泡的影响。在本实验中观察到的结果表明，LPS损害心脏SL的氧自由基机制的产生'OH，由于抑制Na，K-ATP酶活性和脂质过氧化，LPS的效果是不依赖于污染铁的存在。最后，现在必须开始把氧自由基假说的LPS对血管反应性的影响的前景。这仍然是一个开放的调查领域。少