title: Sustained activation of AMPK ameliorates age-associated vascular endothelial dysfunction via a nitric oxide-independent mechanism.
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.
authors.affiliation: Department of Integrative Physiology, University of Colorado at Boulder, 354 UCB, Boulder, CO 80309, USA. Lisa.Lesniewski@utah.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lesniewski
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Zigler
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Durrant
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013113:Spin Labels; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D012265:Ribonucleotides; D013113:Spin Labels; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; C001803:tempol