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.
Department of Legal Medicine, Nara Medical University, Kashihara, Nara, Japan.
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Yuui
Department of Legal Medicine, Nara Medical University, Kashihara, Nara, Japan.
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Kudo
Department of Legal Medicine, Nara Medical University, Kashihara, Nara, Japan.
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Kasuda
Department of Legal Medicine, Nara Medical University, Kashihara, Nara, Japan legalm@naramed-u.ac.jp.
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Hatake
D000818:Animals; D015153:Blotting, Western; D000431:Ethanol / Q000494:pharmacology* / Q000627:therapeutic use; D007022:Hypotension / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications / Q000201:enzymology / Q000276:immunology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D053583:Interleukin-1beta; D000431:Ethanol; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
Ethanol; interleukin-1β; rat; relaxation response; superior mesenteric artery