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标题：Involvement of Inducible Nitric Oxide Synthase in Blood Flow Decrease in Vein Induced by Hen-Egg White Lysozyme
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作者：Hisae Oku ; Yuko Ogawa ; Emiko Iwaoka 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：7
页码：1324-1328
DOI：10.1248/bpb.30.1324
出版社：The Pharmaceutical Society of Japan
摘要：Our in vivo assay system developed to search for allergy-preventive substances, assesses the blood flow decrease in tail vein microcirculation of mice subjected to sensitization with hen-egg white lysozyme (HEL). The blood flow decrease appears to be regulated by various factors such as nitric oxide (NO), thromboxane (TX) A₂, prostacyclin (PGI₂) and endothelin (ET)-1 together with cyclooxygenase (COX)-1, COX-2, inducible nitric oxide synthase (iNOS), and constitutive nitric oxide synthase (cNOS). In this study, we examined in detail the roles of iNOS in this assay system using an iNOS knockout (KO) mouse. We found that the blood flow decrease in the HEL-sensitized iNOS KO mice was slightly weaker than that in their wild type (WT) mice. This blood flow decrease was not affected by a selective COX-1 inhibitor, a selective COX-2 inhibitor and a PGI₂ agonist unlike the case of the WT mice. However, it was inhibited by a nonselective NOS inhibitor, a specific TXA₂ synthase inhibitor and a specific ET-1 receptor blocker as in the case of the WT mice. The present results indicate that the blood flow decrease occurs via two pathways; one is an iNOS-independent response involving TXA₂ and ET-1, and the other is an iNOS-dependent response involving COX-1, COX-2 and PGI₂. cNOS appears to play some roles in the blood flow decrease and iNOS acts as an exacerbation factor. Our method using HEL-sensitized should be useful for searching for agents that can prevent allergy via new mechanisms.
关键词：blood flow;inducible nitric oxide synthase (iNOS);allergy preventive medicine;nitric oxide (NO);hen-egg white lysozyme (HEL)