Abstract
Exercise restores endothelium-dependent dilation (EDD) in old mice by reducing oxidative stress and increasing nitric oxide (NO) bioavailability. Adenosine monophosphate protein kinase (AMPK) activation mimics some effects of exercise. Old (28-30 months) B6D2F1 mice had reduced arterial AMPK expression and superoxide-mediated suppression of EDD vs. young (3-6 months) controls. Pharmacological activation of AMPK by aminoimidazole carboxamide ribonucleotide (AICAR) for 2 weeks increased arterial AMPK and reversed this superoxide-induced impairment of EDD. The improvement in EDD was independent of NO or prostaglandin signaling, suggesting enhanced endothelium-dependent hyperpolarizing factor-related dilation. AMPK activation may represent a novel therapy for treating age-associated vascular dysfunction.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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AMP-Activated Protein Kinases / metabolism*
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Aging / drug effects
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Aging / metabolism*
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Aminoimidazole Carboxamide / analogs & derivatives
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Aminoimidazole Carboxamide / pharmacology
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Animals
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Antioxidants / pharmacology
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Cyclic N-Oxides / pharmacology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / enzymology*
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Mice
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Nitric Oxide / metabolism
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Ribonucleotides / pharmacology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Spin Labels
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Superoxides / antagonists & inhibitors
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Superoxides / metabolism
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Vasodilation / drug effects
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Vasodilation / physiology
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Vasodilator Agents / pharmacology
Substances
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Antioxidants
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Cyclic N-Oxides
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Ribonucleotides
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Spin Labels
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Vasodilator Agents
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Superoxides
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Nitric Oxide
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Aminoimidazole Carboxamide
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AMP-Activated Protein Kinases
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AICA ribonucleotide
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tempol