| Acute negative inotropic effects of homocysteine are mediated via the endothelium. | |
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MedLine Citation:
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PMID: 15072957 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous studies have shown that chronic hyperhomocysteinemia is associated with an adverse cardiac remodeling and heart failure. This study, which utilized coronary-perfused hearts and superfused papillary muscle, was designed to determine whether homocysteine acts acutely to alter cardiac contractile function. Left ventricular developed pressure was used as a measure of systolic function in the Langendorff-perfused heart, whereas isometric developed tension was used in papillary muscle. All preparations were bathed in physiological buffer and paced electrically. Initial results showed that homocysteine elicits a relatively rapid onset (maximum effect observed within 5 min), concentration-dependent (10-300 microM), and moderate negative inotropic action (maximum decrease in tension was approximately 15% of control values) in Langendorff-perfused hearts but not in papillary muscle. In contrast, effluent from homocysteine-treated hearts decreased contractility in papillary muscle, and all inotropic actions were largely eliminated when brief Triton X-100 treatment was utilized to inactivate the coronary endothelium in the intact heart. The homocysteine-induced decrease in contractile function was not antagonized by N(omega)-nitro-l-arginine, a nitric oxide synthase inhibitor, or the cyclooxygenase inhibitor indomethacin. Thus data suggest that pathophysiological concentrations of homocysteine elicit an acute negative inotropic effect on ventricular myocardium that is mediated by a coronary endothelium-derived agent other than nitric oxide or products of cyclooxygenase. Future studies are required to elucidate the mechanism by which homocysteine acts to elicit the release of the proposed endothelial mediator, the identity of the proposed paracrine agent, and the mechanism of its negative inotropic action. |
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Authors:
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Richard H Kennedy; Richard Owings; Nawal Shekhawat; Jacob Joseph |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2004-04-08 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 287 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-07-27 Completed Date: 2004-09-03 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H812-7 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. kennedyrichardh@uams.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiovascular Agents / pharmacology Coronary Vessels / physiology* Drug Synergism Endothelium, Vascular / physiology* Enzyme Inhibitors Heart / drug effects* Homocysteine / pharmacology* Indomethacin / pharmacology Male Myocardial Contraction / drug effects*, physiology* Nitroarginine Octoxynol / pharmacology Papillary Muscles / drug effects, physiology Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Cardiovascular Agents; 0/Enzyme Inhibitors; 2149-70-4/Nitroarginine; 454-28-4/Homocysteine; 53-86-1/Indomethacin; 9002-93-1/Octoxynol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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