Extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) pathways involved in spinal cord stimulation (SCS)-induced vasodilation.
OBJECTIVE
SCS is used to improve peripheral circulation in selected patients with ischemia of the extremities. However the mechanisms are not fully understood. The present study investigated whether blockade of ERK and AKT activation modulated SCS-induced vasodilation.


METHODS
A unipolar ball electrode was placed on the left dorsal column at the lumbar 2-3 spinal segments in rats. Cutaneous blood flows from left and right hind foot pads were recorded with laser Doppler flow perfusion monitors. SCS was applied through a ball electrode at 60% or 90% of MT. U0126, an inhibitor of ERK kinase, or LY294002, an inhibitor of PI3K upstream of AKT, was applied to the lumbar 3-5 spinal segments (n=7, each group).


RESULTS
U0126 (100 nM, 5 microM and 250 microM) significantly attenuated SCS-induced vasodilation at 60% (100 nM: P<0.05; 5 microM and 250 microM: P<0.01, respectively) and 90% of MT (100 nM and 5 microM: P<0.05; 250 microM: P<0.01, respectively). LY294002 at 100 microM also attenuated SCS-induced vasodilation at 60% and 90% of MT (P<0.05).


CONCLUSIONS
These data suggest that ERK and AKT pathways are involved in SCS-induced vasodilation.
Wu
Mingyuan
M
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA.
Komori
Naoka
N
Qin
Chao
C
Farber
Jay P
JP
Linderoth
Bengt
B
Foreman
Robert D
RD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002070:Butadienes / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
D002070:Butadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D009570:Nitriles; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases