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• W1566806909 abstract "Vasodilatation is a vital mechanism of systemic blood flow regulation that occurs during periods of increased energy demand. The AMP-dependent protein kinase (AMPK) is a serine/threonine kinase that is activated by conditions that increase the AMP-to-ATP ratio, such as exercise and metabolic stress. We hypothesized that AMPK could trigger vasodilatation and participate in blood flow regulation. Rings of thoracic aorta were isolated from C57Bl6 mice and mice deficient in the AMPK catalytic α1 (AMPKα1−/−) or α2 (AMPKα2−/−) subunit and their littermate controls, and mounted in an organ bath. Aortas were preconstricted with phenylephrine (1 μm) and activation of AMPK was induced by addition of increasing concentrations of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR). AICAR (0.1–3 mm) dose-dependently induced relaxation of precontracted C57BL6, AMPKα1+/+ and α2+/+ aorta (P < 0.001, n= 5–7 per group). This AICAR induced vasorelaxation was not inhibited by the addition of adenosine receptor antagonists. Moreover, when aortic rings were freed of endothelium by gentle rubbing, AICAR still induced aortic ring relaxation, suggesting a direct effect of AICAR on smooth muscle cells. When aortic rings were pretreated with l-NMMA (30 μm) to inhibit nitric oxide synthase activity, AICAR still induced relaxation. Western blot analysis of C57Bl6 mice denuded aorta showed that AMPK was phosphorylated after incubation with AICAR and that AMPKα1 was the main catalytic subunit expressed. Finally, AICAR-induced relaxation of aortic rings was completely abolished in AMPKα1−/− but not AMPKα2−/− mice. Taken together, the results show that activation of AMPKα1 but not AMPKα2 is able to induce aortic relaxation in mice, in an endothelium- and eNOS-independent manner." @default.
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• W1566806909 date "2007-06-06" @default.
• W1566806909 modified "2023-09-30" @default.
• W1566806909 title "Activation of AMP kinase α1 subunit induces aortic vasorelaxation in mice" @default.
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• W1566806909 doi "https://doi.org/10.1113/jphysiol.2007.132589" @default.
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