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dc.contributor.authorCauwels, Anje
dc.contributor.authorJanssen, Ben
dc.contributor.authorBuys, Emmanuel
dc.contributor.authorSips, Patrick
dc.contributor.authorBrouckaert, Peter
dc.date.accessioned2015-03-18T17:13:59Z
dc.date.issued2006
dc.identifier.citationCauwels, A., Ben Janssen, Emmanuel Buys, Patrick Sips, and Peter Brouckaert. 2006. “Anaphylactic Shock Depends on PI3K and eNOS-Derived NO.” Journal of Clinical Investigation 116 (8) (August 1): 2244–2251. doi:10.1172/jci25426.en_US
dc.identifier.issn0021-9738en_US
dc.identifier.issn1558-8238en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:14229120
dc.description.abstractAnaphylactic shock is a sudden, life-threatening allergic reaction associated with severe hypotension. Platelet-activating factor (PAF) is implicated in the cardiovascular dysfunctions occurring in various shock syndromes, including anaphylaxis. Excessive production of the vasodilator NO causes inflammatory hypotension and shock, and it is generally accepted that transcriptionally regulated inducible iNOS is responsible for this. Nevertheless, the contribution of NO to PAF-induced shock or anaphylactic shock is still ambiguous. We studied PAF and anaphylactic shock in conscious mice. Surprisingly, hyperacute PAF shock depended entirely on NO, produced not by inducible iNOS, but by constitutive eNOS, rapidly activated via the PI3K pathway. Soluble guanylate cyclase (sGC) is generally regarded as the principal vasorelaxing mediator of NO. Nevertheless, although methylene blue partially prevented PAF shock, neither 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) nor sGCα1 deficiency did. Also, in 2 different models of active systemic anaphylaxis, inhibition of NOS, PI3K, or Akt or eNOS deficiency provided complete protection. In contrast to the unsubstantiated paradigm that only excessive iNOS-derived NO underlies cardiovascular collapse in shock, our data strongly support the unexpected concept that eNOS-derived NO is the principal vasodilator in anaphylactic shock and define eNOS and/or PI3K or Akt as new potential targets for treating anaphylaxis.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.isversionofdoi:10.1172/JCI25426en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523420/pdf/JCI0625426.pdfen_US
dash.licenseLAA
dc.titleAnaphylactic shock depends on PI3K and eNOS-derived NOen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of Clinical Investigationen_US
dash.depositing.authorBuys, Emmanuel
dc.date.available2015-03-18T17:13:59Z
dc.identifier.doi10.1172/JCI25426*
dash.contributor.affiliatedSips, Patrick
dash.contributor.affiliatedBuys, Emmanuel


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