Thesis or Dissertation Ethanol attenuates vasorelaxation via inhibition of inducible nitric oxide synthase in rat artery exposed to interleukin-1β.
インターロイキン-1β暴露下のラットの血管におけるエタノールによる誘導型一酸化窒素合成酵素抑制を介した弛緩反応の抑制

Yuui, Katsuya  ,  Kudo, Risa  ,  Kasuda, Shogo  ,  Hatake, Katsuhiko

Epub ahead of printp.pii: 0960327115611944 , 2015-10-22 , SAGE Publications
ISSN:09603271
NCID:AA10758296
Description
Nitric oxide produced by inducible nitric oxide synthase (iNOS) regulates sepsis-induced hypotension. During septic shock, interleukin (IL)-1β is synthesized in endothelial cells and smooth muscle cells by endotoxin. Ethanol (EtOH) suppresses endotoxin-induced hypotension. The present study aimed to elucidate the effect of EtOH on gradual relaxation and iNOS expression induced by IL-1β in isolated rat superior mesenteric arteries (SMAs). Exposure to IL-1β–induced contraction in SMA rings, followed by a gradual relaxation of phenylephrine precontracted tone. Contraction was abolished by indomethacin (IM), cycloheximide (Chx), and endothelium denudation. In contrast, the gradual relaxation was abolished by NOS inhibitors, Chx, endothelium denudation, and inhibited by EtOH (50 and 100 mM). However, IM had no effect on relaxation. Western blot analysis demonstrated that iNOS expression was induced by IL-1β and was inhibited by EtOH and endothelium denudation. Furthermore, messenger RNA expression of iNOS, but not endothelial NOS, was inhibited by EtOH. These data suggest that IL-1β–induced contraction is mediated by thromboxane A2, whereas IL-1β–induced relaxation occurs via NO derived from iNOS. The endothelium plays an important role in vasorelaxation. Taken together, EtOH inhibits IL-1β–mediated vasorelaxation by suppressing endothelium iNOS expression. This study provides the first evidence of EtOH -induced inhibition of IL-1β–mediated vasorelaxation.
博士(医学)・甲第647号・平成28年3月15日
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Copyright © 2016 by SAGE Publications
The definitive version is available at " http://dx.doi.org/10.1177/0960327115611944 "
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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3184/6/03%20%e7%94%b2647%e6%9c%ac%e6%96%87.pdf

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