Sustained activation of AMPK ameliorates age-associated vascular endothelial dysfunction via a nitric oxide-independent mechanism

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• 作者：Lisa A. Lesniewski^a ; ^b ; ^c ; ^{Lisa.Lesniewski@utah.edu} ; Melanie C. Zigler^a ; Jessica R. Durrant^a ; Anthony J. Donato^a ; ^b ; ^c ; Douglas R. Seals^a
• 关键词：ACh ; acetylcholine ; AICAR ; aminoimidazole carboxamide ribonucleotide ; AMPK ; adenosine monophosphate protein kinase ; COX ; cyclooxygenase ; CVD ; cardiovascular disease ; EDD ; endothelium dependent dilation ; EDHF ; endothelial derived hyperpolarizing factor ; l-
• 刊名：Mechanisms of Ageing and Development
• 出版年：2012
• 期刊代码：193_00476374
• 类别：med
• 出版时间：May, 2012
• 卷：133
• 期：5
• 页码：368-371
• 文件大小：491 K

摘要

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.