| Lysozyme binding to endocardial endothelium mediates myocardial depression by the nitric oxide guanosine 3',5' monophosphate pathway in sepsis. | |
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MedLine Citation:
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PMID: 16087190 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inflammatory mediators have been implicated as a cause of reversible myocardial depression in septic shock. We previously reported that the release of lysozyme-c (Lmz-S) from leukocytes from the spleen or other organs contributes to myocardial dysfunction in Escherichia coli septic shock in dogs by binding to a cardiac membrane glycoprotein. However, the mechanism by which Lzm-S causes this depression has not been elucidated. In the present study, we tested the hypothesis that the binding of Lzm-S to a membrane glycoprotein causes myocardial depression by the formation of nitric oxide (NO). NO generation then activates soluble guanylyl cyclase and increases cyclic guanosine monophosphate (cGMP), which in turn triggers contractile impairment via activation of cGMP-dependent protein kinase (PKG). We examined these possibilities in a right ventricular trabecular preparation in which isometric contraction was used to measure cardiac contractility. We found that Lzm-S's depressant effect could be prevented by the non-specific NO synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA). A guanylyl cyclase inhibitor (ODQ) and a PKG inhibitor (Rp-8-Br-cGMP) also attenuated Lzm-S's depressant effect as did chemical denudation of the endocardial endothelium (EE) with Triton X-100 (0.5%). In EE tissue, we further showed that Lzm-S caused NO release with use of 4,5 diaminofluorescein, a fluorescent dye that binds to NO. The present study shows that the binding of Lzm-S to EE generates NO, and that NO then activates the myocardial guanosine 3',5' monophosphate pathway leading to cardiac depression in sepsis. |
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Authors:
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Steven N Mink; Ratna Bose; Diane E Roberts; Hans Jacobs; Krika Duke; Deepak Bose; Zhao-Qin Cheng; R Bruce Light |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of molecular and cellular cardiology Volume: 39 ISSN: 0022-2828 ISO Abbreviation: J. Mol. Cell. Cardiol. Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-09-26 Completed Date: 2005-11-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0262322 Medline TA: J Mol Cell Cardiol Country: England |
Other Details:
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Languages: eng Pagination: 615-25 Citation Subset: IM |
Affiliation:
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Department of Medicine, Health Sciences Center, University of Manitoba, 700 William Avenue, Winnipeg, Mannitoba, Canada. minksn@cc.umanitoba.ca |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Membrane / metabolism Cyclic GMP / analogs & derivatives, metabolism*, pharmacology Dogs Endocardium / cytology, drug effects, metabolism* Endothelium / drug effects, metabolism Muramidase / metabolism, pharmacology* Myocardial Contraction* / drug effects Myocardium / metabolism Nitric Oxide / metabolism* Oxadiazoles / pharmacology Quinoxalines / pharmacology Sepsis / metabolism*, physiopathology* omega-N-Methylarginine / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/Oxadiazoles; 0/Quinoxalines; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 31356-94-2/8-bromocyclic GMP; 7665-99-8/Cyclic GMP; EC 3.2.1.17/Muramidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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