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AMPK ACTIVATORS REGULATE CONTRACTILE FUNCTION OF MESENTERIC ARTERIES

Vasoconstrictor tone in the splanchnic circulation redistributes blood flow during hemorrhage and resuscitation. A metabolic sensor, 5’adenosine monophosphate-activated protein kinase (AMPK), has been proposed to relax arteries by inhibiting myosin light chain (MLC) kinase (MLCK) and rho kinase (ROCK) activities. Because AMPK activation might be beneficial in re-establishing splanchnic blood flow during resuscitation, we sought to explore the relative ability of AMPK activators (AICAR, A769662, berberine (BBR) and simvastatin (SIMV)) to relax mesenteric artery (MA) contraction. Our data revealed that these drugs caused vasorelaxation when tissues were stimulated either with KCl (producing primarily a Ca2+ dependent contraction) or phenylephrine (PE; producing a primarily Ca2+ independent contraction). We further investigated the potential mechanisms by which BBR induced mesenteric artery relaxation. We found that BBR did not inhibit MLC phosphorylation, nor did it phosphorylate AMPK, and therefore is likely working through another mechanism to cause vasorelaxation. Notably, PE induced an increase in AMPK phosphorylation and, of all the AMPK activators examined, only AICAR phosphorylated AMPK in rabbit mesenteric artery, which provides a guide for future studies.

Identiferoai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-4331
Date21 April 2014
CreatorsLocke, Victoria
PublisherVCU Scholars Compass
Source SetsVirginia Commonwealth University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses and Dissertations
Rights© The Author

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