AMPK Activators Cause Different Vasoconstrictor Responses in Small and Large Muscular Arteries

The metabolic sensor/effector AMP kinase (AMPK) responds to vasoconstrictors and metabolic stress, but the role of these stimuli and AMPK activators to modulate AMPK in large and small arteries during trauma is unclear. We tested the ability of multiple agents (angiotensin II (Ang II), phenylephrine (PE), U-46619 (U-46) and vasopressin (VP)) to contract femoral (FA) or epigastric (EA) vessels with or without classic (AICAR, A769662) or putative (metformin (MET), berberine (BBR), simvastatin (SIM)) AMPK agonists. Artery rings were removed from euthanized rabbits and secured to a wire myograph for tension analyses. Tissues were quick-frozen and processed to measure AMPK-pT172, Raptor-pS792, MLC-p20, and MYPT-pT850. Compared to EA, FA responded strongly and potently to all agents. In FA but not EA, AICAR caused a significant right shift in the PE and U46-induced phasic concentration-response curve (CRC), but inhibited steady-state (30 min) tension induced by PE in EA. AMPK-pT172 and Raptor-pS792 significantl...