Phathophysiology of Circulatory Failure in Oral Region : Its Pharmacological Analysis

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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