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

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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