2000 Fiscal Year Final Research Report Summary
PROTECTIVE EFFECT OF PROPOFOL ON FREE RADICAL INDUCED IMPAIRMENT OF VASCULAR SMOOTH MUSCLE REACTIVITY.
| Project/Area Number |
10671756
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | KANAGAWA DENTAL COLLEGE |
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Principal Investigator |
KOBAYASHI Yutaka KANAGAWA DENTAL COLLEGE, DEPARTMENT OF ORAL PHYSIOLOGY, ASSISTANT PROFESSOR, 歯学部, 講師 (50130919)
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| Co-Investigator(Kenkyū-buntansha) |
SYOUJI Hirofumi KANAGAWA DENTAL COLLEGE, DEPARTMENT OF PHARMACOLOGY, INSTRUCTOR, 歯学部, 助手 (90277913)
TODOKI Kazuo KANAGAWA DENTAL COLLEGE, DEPARTMENT OF PHARMACOLOGY, ASSISTANT PROFESSOR, 歯学部, 講師 (90139577)
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| Project Period (FY) |
1998 – 2000
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| Keywords | PROPOFOL / VASCULAR SMOOTH MUSCLE / REACTIVE OXYGEN SPECIES / α-ADRENOCEPTOR / ENDOTHELIAL CELL |
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| Research Abstract |
Propofol (2,6-diisopropylohenol) has been shown to attenuate oxidative stress-induced tissue injury. However, little is known concerning the effects of propofol on the reactive oxygen species-induced impairment of vascular reactivity. Therefore, this study was designed to examine the effect of propofol on reactive oxygen species-induced modification of the α-adrenoceptor mediated vascular contraction and in endothelium-dependent relaxation responses of the isolated blood vessels. The ring preparations of mesenteric artery from male albino rabbits were suspended in 10 ml organ baths containing modified Krebs-Ringer solution and changes in isometric force were measured. Effects of prior exposure the ring preparations to hydroxyl radical (HO) generated from Fenton's reagent (150 μM H_2O_2 plus 100 μM FeSO_4), hydrogen peroxide (H_2O_2 ; 150 μM) and FeSO_4 (100 μM ) on norepinephrine (NE ; 1μM)-induced contraction and acetylcholine (ACh ; 1 μM)-induced relaxation and protective effects of
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propofol were investigated. In addition, free radical scavenging property of propofol was also assessed using luminol-enhanced chemiluminescence method and electron spin resonance (ESR) spectroscopy. Prior exposure of ring preparations to HO and H_2O_2 inhibited NE-induced tension development to 47.0 ± 8.05 % and 40.2 ± 2.78 % of control values, respectively. Exposure the ring preparation to FeSO4 alone was without effect. While propofol, concentration of 10μM potentiated the NE-induced contraction by itself, it protected against the observed inhibitory effect on NE-induced contractile responses by Fenton's reagent and H_2O_2 to 97.4 ± 3.54 and 90.4 ± 4.20, respectively. Incubation of ring preparations with Krebs-Ringer solution containing Fenton's reagent and H_2O_2 inhibited ACh-induced relaxation to 79.8 ± 2.63 % and 73.0±2.77% of control values, respectively. Exposure the ring preparation to FeSO_4 alone was without effect. Propofol (10 μM, which has no effect on ACh-induced relaxation by itself) protected against the observed inhibitory effect on ACh-induced endothelium-dependent relaxation by HO or H_2O_2. Both Fenton's reagent- and H_2O_2-induced enhancements of luminol-chemilumionescence were attenuated by addition of propofol in a dose-dependent manner. Analysis of ESR spectroscopy provided the evidence that propofol and Diprivan【○!R】 in concentration of 1 and 10 μM, respectively, inhibited the formation of DMPO-HO spin adducts in a dose-dependently. Results obtained in present study demonstrated that clinically relevant concentration of propofol could protect against the impairment of vascular reactivity of isolated rabbit mesenteric artery induced by reactive oxygen species probably due to its scavenging ability of hydrogen peroxide. Less
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