| Project/Area Number |
11670723
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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 |
Circulatory organs internal medicine
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| Research Institution | Kurume University School of Medicine |
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Principal Investigator |
MATSUOKA Hidehiro Kurume Univ. School of Medicine, Dept. of Internal Medicine III, Assistant Professor, 医学部, 講師 (80248393)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Hiroshi Kurume Univ. School of Medicine, Dept. of Nephrology, Instructor, 医学部, 助手 (80279174)
KATO Seiya Kurume Univ. School of Medicine, Dept. of Pathology, Associate Professor, 医学部, 助教授 (60268844)
IKEDA Hisao Kurume Univ. School of Medicine, Dept. of Internal Medicine III, Associate Professor, 医学部, 助教授 (50168134)
USUI Michiaki Kurume Univ. School of Medicine, Dept. of Nephrology, Instructor, 医学部, 助手 (50279163)
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| Project Period (FY) |
1999 – 2000
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| Keywords | nitric oxide synthase / smoking / monomethyl-L-arginine / flow-mediated vasodilation / endothelium / 危険因子 / 血小板 / 葉酸 |
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| Research Abstract |
In smokers, endothelium-derived NO bioactivity is impaired. BH4 is an essential co-factor of NO synthase, and its deficiency decreases NO bioactivity. The aim of this study was to test whether tetrahydrobiopterin (BH4) supplementation improves nitric oxide (NO) bioactivity in smokers. Sapropterin hydrochloride, an active analogue of BH4 (2 mg/kg), was administrated orally to healthy male smokers and age-matched non-smokers. Before and at 3- and 24-hours after sapropterin, we measured plasma levels of BH4 and examined flow-mediated vasodilation (FMD) of the brachial artery by high resolution ultrasonography, a non-invasive test of endothelial function. Basal plasma levels of BH4 were not different between smokers and non-smokers. Sapropterin administration increased plasma levels of BH4 by 3-fold at 3-hour, which returned to the baseline at 24-hour. Before sapropterin, FMD was significantly smaller in smokers (p=0.0002). Sapropterin significantly augmented endothelium-dependent vasodilation in smokers, but did not affect it in non-smokers (p=0.001 by ANOVA). Co-administration of N^G-monomethyl-L-arginine (L-NMMA), an NOS inhibitor (20 μmol), into the brachial artery completely abolished the vasodilatory effects of sapropterin (p=0.002 by ANOVA). Endothelium-independent vasodilation by glyceryl trinitrate was not different between smokers and non- smokers, and was not altered by BH4. We demonstrated that the BH4 supplementation improved bioactivity of endothelium-derived NO in smokers. These observations strongly suggest that decreased NO-dependent vasodilation in smokers could be related to reduced bioactivity of BH4.
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