DOI
https://doi.org/10.25772/CMVJ-C110
Defense Date
2014
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Paul Ratz
Abstract
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.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
May 2014