| trans-Arachidonic acids induce a heme oxygenase-dependent vasorelaxation of cerebral microvasculature. | |
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MedLine Citation:
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PMID: 18082639 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nitrative stress is an important regulator of vascular tone. We have recently described that trans-arachidonic acids (TAA) are major products of NO(2)(.)-mediated isomerization of arachidonic acid in cell membranes and that nitrative stress increases TAA levels leading to neural microvascular degeneration. In the present study, we explored whether TAA exert acute effects on neuromicrovascular tone and investigated potential mechanisms thereof. TAA induced an endothelium-dependent vasorelaxation of rat brain pial microvasculature. This vasorelaxation was independent of nitric oxide, prostanoids, lipoxygenase products, and CYP(450) metabolite trans-hydroxyeicosatetraenoic acids. However, inhibition of heme oxygenase (using zinc protoporphyrin IX) and of dependent soluble guanylate cyclase (sGC; using ODQ) significantly diminished (by approximately 70%) the TAA-induced vasorelaxation. Consistent with these findings, TAA stimulated heme oxygenase (HO)-2-dependent bilirubin (using siRNA HO-2) and cGMP formation, and the HO product carbon monoxide (using CO-releasing CORM-2) reproduced the sGC-dependent cGMP formation and vasorelaxation. Further exploration revealed that TAA-induced vasorelaxation and bilirubin formation (HO activation) were nearly abrogated by large-conductance calcium-dependent potassium channels (BK(Ca)) (using TEA and iberiotoxin). Opening of BK(Ca) with the selective activator NS1619 induced a concentration-dependent vasorelaxation, which was inhibited by HO and sGC inhibitors. Coimmunoprecipitation suggested a molecular complex interaction between BK(Ca) and HO-2 (but not HO-1). Collectively, these findings identify new properties of TAA, specifically cerebral vasorelaxation through interactive activation of BK(Ca) with HO-2 and, in turn, sGC. Our findings provide new insights into the characterization of nitrative stress-derived TAA products, by showing they can act as acute mediators of nitrative stress on neurovascular tone. |
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Authors:
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Amna Kooli; Elsa Kermorvant-Duchemin; Florian Sennlaub; Michela Bossolasco; Xin Hou; Jean-Claude Honoré; Phyllis A Dennery; Przemyslaw Sapieha; Daya Varma; Pierre Lachapelle; Tang Zhu; Sophie Tremblay; Pierre Hardy; Kavita Jain; Michael Balazy; Sylvain Chemtob |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-11-28 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 44 ISSN: 0891-5849 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-02-12 Completed Date: 2008-04-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 815-25 Citation Subset: IM |
Affiliation:
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Department of Paediatrics, Research Center of Hôpital Ste-Justine, Montréal, Quebec, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arachidonic Acids / chemistry, pharmacology* Bilirubin / metabolism Cells, Cultured Cerebrovascular Circulation / drug effects*, physiology Cyclic AMP / metabolism Cyclic GMP / metabolism Endothelium, Vascular / cytology, metabolism Heme Oxygenase (Decyclizing) / metabolism* Immunoenzyme Techniques Immunoprecipitation Nitrites / metabolism Potassium Channels / metabolism RNA, Messenger / genetics, metabolism Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction Stereoisomerism Vasodilation / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 0/BKCa protein, rat; 0/Nitrites; 0/Potassium Channels; 0/RNA, Messenger; 60-92-4/Cyclic AMP; 635-65-4/Bilirubin; 7665-99-8/Cyclic GMP; EC 1.14.99.3/Heme Oxygenase (Decyclizing) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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