| Nitric oxide depresses connexin 43 after myocardial infarction in mice. | |
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MedLine Citation:
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PMID: 18394025 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: Heart failure (HF) is a major cause of death and morbidity. Connexin 43 (Cx43) content is reduced in the failing myocardium, but regulating factors have not been identified. In HF, inducible nitric oxide synthase (iNOS)-induced high levels of nitric oxide (NO) cause apoptosis and cardiac dysfunction. However, a direct iNOS-Cx43 link has not been demonstrated. We investigated this relationship in mice after myocardial infarction. METHODS: Effects of myocardial infarction were evaluated 2 weeks after coronary artery ligation in wild-type C57BL/6 (WT) and iNOS(-/-) knockout mice. Myocardial Cx43 and Cx45 content were assessed by immunofluorescence confocal imaging and western blotting. Cardiac function was evaluated in anaesthetized mice using a micro pressure-tipped catheter inserted into the left ventricle. RESULTS: Despite similar infarct size, deficiency in iNOS resulted in significantly lower plasma nitrate/nitrite levels, better haemodynamic performance and lower mortality 2 weeks after coronary ligation. Myocardial Cx43, but not Cx45, content was lower in WT mice following ligation. The reduction in Cx43 was less in iNOS(-/-) compared with WT mice. To assess the direct effect of NO on Cx43 expression, cultured neonatal mouse cardiomyocytes were employed. Incubation with the NO donor, S-nitroso-N-acetylpenicillamine, elicited a dose-dependent decrease in Cx43 content in cultured neonatal cardiomyocytes. CONCLUSIONS: Increased NO production from iNOS depressed cardiac performance and contributed to the decreased myocardial Cx43 content 2 weeks after myocardial infarction. |
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Authors:
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P E M Jackson; Q P Feng; D L Jones |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-04-03 |
Journal Detail:
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Title: Acta physiologica (Oxford, England) Volume: 194 ISSN: 1748-1716 ISO Abbreviation: Acta Physiol (Oxf) Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-08-12 Completed Date: 2008-10-03 Revised Date: 2011-10-27 |
Medline Journal Info:
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Nlm Unique ID: 101262545 Medline TA: Acta Physiol (Oxf) Country: England |
Other Details:
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Languages: eng Pagination: 23-33 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Western Ontario, London, ON, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Blotting, Western / methods Cells, Cultured Connexin 43 / analysis, metabolism* Depression, Chemical Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Confocal Models, Animal Myocardial Infarction / metabolism* Myocardium / metabolism* Myocytes, Cardiac / drug effects, metabolism Nitric Oxide / metabolism* Nitric Oxide Synthase Type II / antagonists & inhibitors*, genetics, metabolism Random Allocation S-Nitroso-N-Acetylpenicillamine / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Connexin 43; 10102-43-9/Nitric Oxide; 79032-48-7/S-Nitroso-N-Acetylpenicillamine; EC 1.14.13.39/NOS2 protein, human; EC 1.14.13.39/Nitric Oxide Synthase Type II |
| Comments/Corrections | |
Comment In:
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Acta Physiol (Oxf). 2008 Sep;194(1):1
[PMID:
18694420
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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