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1 Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA; Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA; Centers for Diabetes and Cardiovascular Helath and Gener Physiology and Environmental Adaptations, University of Missouri, Columbia, MO, USA
2 Department of Medical Pharmacology & Physiology, University of Missouri, Columbia, MO, USA
3 Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA
4 Department of Medical Pharmacology & Physiology, University of Missouri, Columbia, MO, USA; Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA; Centers for Diabetes and Cardiovascular Helath and Gener Physiology and Environmental Adaptations, University of Missouri, Columbia, MO, USA
5 Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA; Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
* To whom correspondence should be addressed. E-mail: RubinL{at}missouri.edu.
AMP-activated kinase (AMPK) is a highly conserved heterotrimeric kinase that functions as a metabolic master switch to coordinate cellular enzymes involved in carbohydrate and fat metabolism that regulate ATP conservation and synthesis. AMPK is activated by conditions that increase AMP to ATP ratio (AMP/ATP), such as exercise and metabolic stress. In the current study, we probed whether AMPK was expressed in vascular smooth muscle and would be activated by metabolic stress. Endothelium denuded porcine carotid artery segments were metabolically challenged with 2-deoxyglucose (10 mM) plus nitrogen (N2/2DG). These vessels exhibited a rapid increase in AMPK activity by 1 minute that was near maximal by 20 minutes. AMPK inactivation on return to normal physiological saline was ~50 percent in 1 minute and fully recovered by 5 minutes. Immunoprecipitation of the 
1 and 2 catalytic subunit followed by immunoblot analysis for [P]Thr172-AMPK indicates that 1-AMPK accounts for all activity. Little if any 2-AMPK was detected in carotid smooth muscle. AMPK activity was not increased by contractile agonist (endothelin-1) nor by the reported AMPK activators, 5-aminoimidazole-4-carboxamide-riboside (AICAR, 2 mM), metformin (2 mM) or phenformin (0.2 mM). AMPK activation by N2/2DG was associated with a rapid and pronounced reduction in endothelin-induced force and reduced phosphorylation of Akt and Erk1/2. These data demonstrate that AMPK expression differs in vascular smooth muscle compared to striated muscles and that activation and inactivation following metabolic stress occurs rapidly and is associated with signaling pathways that may regulate smooth muscle contraction.
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