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标题：Hypotensive Effect of FAD and Its Mechanism: Involvement of Nitric Oxide Synthase Activation
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作者：Akiko HASHIDA-OKUMURA ; Katsuya NAGAI ; Nobuaki OKUMURA 等
期刊名称：Journal of Clinical Biochemistry and Nutrition
印刷版ISSN：0912-0009
电子版ISSN：1880-5086
出版年度：1995
卷号：18
期号：2
页码：97-109
DOI：10.3164/jcbn.18.97
出版社：The Society for Free Radical Research Japan
摘要：Flavin adenine dinucleotide (FAD) is one of the cofactors of nitric oxide synthase (NOS). Recently, we found that FAD acted as an allosteric activator of holo NOS of the neuronal type. In the present study, we obtained the following results in rats: 1) FAD enhanced cyclic GMP (cGMP) production in primary cultures of neuronal cells and its effect was completely abolished by preincubation of the cells with a potent inhibitor of NOS, N^G-monomethyl-L-arginine. 2) FAD injection into the lateral cerebral ventricle decreased the blood pressure and heart rate. This effect was suppressed by preadministration of N^G-monomethyl-L-arginine. 3) The reduction in the blood pressure and heart rate by FAD was accompanied by suppression of the neural activity of the sympathetic efferents to the kidney. This effect was blocked by preadministration of N^G-monomethyl-L-arginine. 4) Intravenous injection of FAD also caused reductions in the blood pressure and heart rate. These results suggest that FAD activates NOS in neuronal cells and that the resultant NO reduces the blood pressure by suppressing sympathetic nerve activity. We also obtained evidence that FAD regulates the cardiovascular system when administered peripherally.
关键词：cyclic GMP;blood pressure;sympathetic nervous system;nitric oxide;primary cultures of neuronal cells