LEE Chang-il Kanagawa Dental College, Pharmacology, Instructor, 歯学部, 助手 (60220795)
TAKAHASHI Shunsuke Kanagawa Dental College, Pharmacology, Instructor, 歯学部, 助手 (60206810)
TODOKI Kazuo Kanagawa Dental College, Pharmacology, Assistant Professor, 歯学部, 講師 (90139577)
伊藤 春生 神奈川歯科大学, 歯学部, 教授 (10084716)
|Budget Amount *help
¥7,100,000 (Direct Cost : ¥7,100,000)
Fiscal Year 1996 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1995 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1994 : ¥4,700,000 (Direct Cost : ¥4,700,000)
The physiological importance of the oxygen free radical system was revealed by the discovery that activated neutrophils produce the superoxide anion radical (O_2^<・->). The O_2^<・-> cascade (producing H_2O_2 and hydroxylradical, HO・) established in basic chemistry stimulated investigators of reactive oxygen species in numerous pathophysiological processes. The first target of reactive oxygen species, generated in several pathological processes, is the vascular system. In this research project, we wished to investigate the mechanisms of the effect of reactive oxygen species on vascular smooth muscle at the cellular level.
1. The HO・radical directly produces vasoconstriction in the dental pulp in dogs. This could be explained by the destruction of basally released endothelium-derived relaxing factor, possibly nitric oxide, and/or endothelial dysfunction. The selective effect of this radical on endothelium-dependent relaxation of pulpal vessels is supported by the finding that the increase
in blood flow caused by a direct-acting, endothelium-independent dilator, nitroglycerin, but not by acetylcholine, was unaffected by the exposure to the HO・radical.
2. We found that canine lingual artery are innervated by calcitonin gene-related peptide (CGRP)-containing vasodilator nerves. The HO・radical, rather than H_2O_2, to be the active agent in disturbance of CGRP-mediated neurogenic relaxiation, and it can be suggested that HO・can deplete endogenous CGRP localized prejunctionally and also damage CGRP-induced relaxation of canine lingual artery that is caused by activation of ATP-sensitive K^+ channels at postjunctional sites.
3. We evaluated the effects of reactive oxygen species on contractions induced by caffeine, Ins (1,4,5) P_3 and noradrenaline (NA) in Staphylococcal alpha-toxin-permeabilized rabbit mesenteric artery. The pathway of Ca^<2+> release from sarcoplasmic reticulum (SR) dependent on Ins (1,4,5) P_3 is insensitive to O_2^<・->. Instead, caffeine-induced Ca^<2+> release mechanism may be susceptible to O_2^<・->, and H_2O_2, rather than O_2^<・-> and HO・, may be the active agent in the NA-induced contraction. The results obtained are also consistent with the view that the attenuation by H_2O_2 of the NA-induced contraction may be linked to the receptor-associated pathway of Ins (1,4,5) P_3 formation.
We also assessed the effect of singlet oxygen (^1O_2) on vascular reactivity of rabbit mesenteric artery ring preparations. ^1O_2 generated from photolysis of rose bengal is the potent destracive oxygen.****. Endothelium-dependent relaxation is quite vulnerable to ^1O_2 is depresses NA-induced contraction possibly via alpha-adrenoceptor dysfunction.
If the sequence of events during pathophysiological processes such as periodontitis in the vascular wall as well (especially in endothelial cells), it may lead to disturbances of regional blood flow, which may aggravate the tissue injury.