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

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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.