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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...
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Published in: | Human & experimental toxicology 2016-09, Vol.35 (9), p.938-945 |
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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. |
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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.</description><identifier>ISSN: 0960-3271</identifier><identifier>EISSN: 1477-0903</identifier><identifier>DOI: 10.1177/0960327115611944</identifier><identifier>PMID: 26500219</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Blotting, Western ; Ethanol - pharmacology ; Ethanol - therapeutic use ; Hypotension - enzymology ; Hypotension - etiology ; Hypotension - prevention & control ; In Vitro Techniques ; Interleukin-1beta - pharmacology ; Male ; Mesenteric Artery, Superior - drug effects ; Mesenteric Artery, Superior - enzymology ; Mesenteric Artery, Superior - immunology ; Nitric Oxide Synthase Type II - antagonists & inhibitors ; Nitric Oxide Synthase Type II - genetics ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Sepsis - complications ; Sepsis - enzymology ; Sepsis - immunology ; Vasoconstriction - drug effects ; Vasodilation - drug effects</subject><ispartof>Human & experimental toxicology, 2016-09, Vol.35 (9), p.938-945</ispartof><rights>The Author(s) 2015</rights><rights>The Author(s) 2015.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4554-8bf11456375c35158bd15dcacd7b4c71758c9e14a53ab245d20140a6b828b0393</citedby><cites>FETCH-LOGICAL-c4554-8bf11456375c35158bd15dcacd7b4c71758c9e14a53ab245d20140a6b828b0393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0960327115611944$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0960327115611944$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21946,27832,27903,27904,44924,45312</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/0960327115611944?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26500219$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuui, K</creatorcontrib><creatorcontrib>Kudo, R</creatorcontrib><creatorcontrib>Kasuda, S</creatorcontrib><creatorcontrib>Hatake, K</creatorcontrib><title>Ethanol attenuates vasorelaxation via inhibition of inducible nitric oxide synthase in rat artery exposed to interleukin-1β</title><title>Human & experimental toxicology</title><addtitle>Hum Exp Toxicol</addtitle><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.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Ethanol - pharmacology</subject><subject>Ethanol - therapeutic use</subject><subject>Hypotension - enzymology</subject><subject>Hypotension - etiology</subject><subject>Hypotension - prevention & control</subject><subject>In Vitro Techniques</subject><subject>Interleukin-1beta - pharmacology</subject><subject>Male</subject><subject>Mesenteric Artery, Superior - drug effects</subject><subject>Mesenteric Artery, Superior - enzymology</subject><subject>Mesenteric Artery, Superior - immunology</subject><subject>Nitric Oxide Synthase Type II - antagonists & inhibitors</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Rats, Wistar</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Sepsis - complications</subject><subject>Sepsis - enzymology</subject><subject>Sepsis - immunology</subject><subject>Vasoconstriction - drug effects</subject><subject>Vasodilation - drug effects</subject><issn>0960-3271</issn><issn>1477-0903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNp1kM1uFDEQhC0EIpuEOyfkI5cB94w99hxRFH6kSFzCedT29CYOs_Zie6JdKU_Fg_BM8bKBAxKnVnVVf1IXY69BvAPQ-r0YetG1GkD1AIOUz9gKpNaNGET3nK0OdnPwT9hpzndCiH5Q8JKdtL0SooVhxR4uyy2GOHMshcKChTK_xxwTzbjD4mPg9x65D7fe-t8yrquaFuftTDz4krzjcecn4nkfKixT9XnCwjEVSntOu23MNPESq1E3My3ffWjg189z9mKNc6ZXT_OMfft4eX3xubn6-unLxYerxkmlZGPsGkCqvtPKdQqUsROoyaGbtJVOg1bGDQQSVYe2lWpqBUiBvTWtsaIbujP29sjdpvhjoVzGjc-O5hkDxSWPYACMNl1valQcoy7FnBOtx23yG0z7EcR46Hz8t_N68uaJvtgNTX8P_pRcA80xkPGGxru4pFC__T_wETXSiyQ</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Yuui, K</creator><creator>Kudo, R</creator><creator>Kasuda, S</creator><creator>Hatake, K</creator><general>SAGE Publications</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7ST</scope><scope>7U7</scope><scope>C1K</scope><scope>SOI</scope></search><sort><creationdate>20160901</creationdate><title>Ethanol attenuates vasorelaxation via inhibition of inducible nitric oxide synthase in rat artery exposed to interleukin-1β</title><author>Yuui, K ; Kudo, R ; Kasuda, S ; Hatake, K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4554-8bf11456375c35158bd15dcacd7b4c71758c9e14a53ab245d20140a6b828b0393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Ethanol - pharmacology</topic><topic>Ethanol - therapeutic use</topic><topic>Hypotension - enzymology</topic><topic>Hypotension - etiology</topic><topic>Hypotension - prevention & control</topic><topic>In Vitro Techniques</topic><topic>Interleukin-1beta - pharmacology</topic><topic>Male</topic><topic>Mesenteric Artery, Superior - drug effects</topic><topic>Mesenteric Artery, Superior - enzymology</topic><topic>Mesenteric Artery, Superior - immunology</topic><topic>Nitric Oxide Synthase Type II - antagonists & inhibitors</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Rats, Wistar</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Sepsis - complications</topic><topic>Sepsis - enzymology</topic><topic>Sepsis - immunology</topic><topic>Vasoconstriction - drug effects</topic><topic>Vasodilation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuui, K</creatorcontrib><creatorcontrib>Kudo, R</creatorcontrib><creatorcontrib>Kasuda, S</creatorcontrib><creatorcontrib>Hatake, K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><jtitle>Human & experimental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Yuui, K</au><au>Kudo, R</au><au>Kasuda, S</au><au>Hatake, K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ethanol attenuates vasorelaxation via inhibition of inducible nitric oxide synthase in rat artery exposed to interleukin-1β</atitle><jtitle>Human & experimental toxicology</jtitle><addtitle>Hum Exp Toxicol</addtitle><date>2016-09-01</date><risdate>2016</risdate><volume>35</volume><issue>9</issue><spage>938</spage><epage>945</epage><pages>938-945</pages><issn>0960-3271</issn><eissn>1477-0903</eissn><abstract>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.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>26500219</pmid><doi>10.1177/0960327115611944</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Blotting, Western Ethanol - pharmacology Ethanol - therapeutic use Hypotension - enzymology Hypotension - etiology Hypotension - prevention & control In Vitro Techniques Interleukin-1beta - pharmacology Male Mesenteric Artery, Superior - drug effects Mesenteric Artery, Superior - enzymology Mesenteric Artery, Superior - immunology Nitric Oxide Synthase Type II - antagonists & inhibitors Nitric Oxide Synthase Type II - genetics Rats, Wistar Real-Time Polymerase Chain Reaction Sepsis - complications Sepsis - enzymology Sepsis - immunology Vasoconstriction - drug effects Vasodilation - drug effects |
title | Ethanol attenuates vasorelaxation via inhibition of inducible nitric oxide synthase in rat artery exposed to interleukin-1β |
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