Abstract
To examine the role of p66shc in endothelial dysfunction, we investigated the endothelium-dependent relaxation, protein expression and superoxide production in abdominal aortic coarctation rats. Endothelium-dependent relaxation to acetylcholine was impaired only in the aortic segments above the aortic coarctation (35.0+/-7.1% vs. 86.6+/-6.0% for sham control at 1 microM Ach). The aortic segments exposed to increased blood pressure showed a decreased phosphorylation of endothelial nitric oxide synthase, an increased phosphorylation of p66shc, and an increased superoxide production. Angiotensin II elicited a significantly increased phosphorylation of p66shc in the endothelial cells. Taken together, these findings suggest that the increased phosphorylation of p66shc is one of the important mediators in the impaired endothelium-dependent relaxation of aortic coarctation rats.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism*
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Angiotensin I / pharmacology
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Animals
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Aortic Coarctation / complications
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Aortic Coarctation / physiopathology*
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Disease Models, Animal
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Endothelium, Vascular / metabolism
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Endothelium, Vascular / physiopathology*
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Hypertension / etiology
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Hypertension / physiopathology*
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Mice
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Nitric Oxide Synthase Type III / metabolism
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Phosphorylation / drug effects
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Rats
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Rats, Sprague-Dawley
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Shc Signaling Adaptor Proteins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Superoxide Dismutase / metabolism
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Superoxides / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Shc Signaling Adaptor Proteins
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Shc1 protein, mouse
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Shc1 protein, rat
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Superoxides
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Angiotensin I
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Nitric Oxide Synthase Type III
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Superoxide Dismutase