Ethanol attenuates vasorelaxation via inhibition of inducible nitric oxide synthase in rat artery exposed to interleukin-1β.

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;© The Author(s);Copyright © 2016 by SAGE Publications;The definitive version is available at " http://dx.doi.org/10.1177/0960327115611944 ";開始ページ : pii: 0960327115611944;PubMed番号 : http://www.ncbi.nlm.nih.gov/pubmed/26500219

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書名 Ethanol attenuates vasorelaxation via inhibition of inducible nitric oxide synthase in rat artery exposed to interleukin-1β.
著作者等 British Toxicology Society
Hatake Katsuhiko
Kasuda Shogo
Kudo Risa
Yuui Katsuya
書名別名 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
出版元 Sage
刊行年月 c1990-
ページ数 v.
大きさ 25 cm
ISSN 09603271
NCID AA10758296
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言語 英語
出版国 イギリス
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