Role of p38 mitogen-activated protein kinases in cardioprotection of morphine preconditioning.
BACKGROUND
p38 mitogen-activated protein kinases (MAPK) in ischemic preconditioning (IPC) may be essential to cardioprotection. We assessed whether protective effect of morphine-induced preconditioning (MPC) on myocardial ischemia and reperfusion injury in rat hearts involved p38 MAPK activation.


METHODS
Male Spargue-Dawley rats (weighing 300-350 g) were randomly assigned to 1 of the following 8 groups: control (CON, saline vehicle, n=9), SB 203580 (SB, a p38 MAPK inhibitor, n=6), MPC (n=6), IPC (n=9), SB+MPC, SB+IPC, MPC+SB, and IPC+SB (n=6). Infarct sizes (IS), a percentage of the area at risk (AAR), were determined by triphenyltetrazolium (TTC) staining. Tissue samples were processed from the entire AAR of left ventricle for the determination of p38 MAPK protein expression (5 hearts/group). The bands representing the proteins were visualized using an enhanced chemiluminescence detection system.


RESULTS
The IS/AAR was significantly reduced by IPC (12.9+/-1.6)% or MPC (25.3+/-2.9)% compared to the control (52.7+/-5.5)%. SB 203580 administered prior to preconditioning abolished the effect of IPC (SB+IPC: (43.8+/-2.6)%, P>0.05 vs CON, P<0.01 vs IPC), but not MPC (SB+MPC: (30.7+/-0.9)%, P<0.01 vs CON, P>0.05 vs MPC). Treatment with SB 203580 prior to sustained ischemia diminished the protective effect of both MPC (MPC+SB: (42.4+/-2.9)%, P>0.05 vs CON) and IPC (IPC+SB: (52.0+/-2.5)%, P>0.05 vs CON) on IS/AAR. In the IPC group, phospho-p38 MAPK protein increased significantly within 5 minutes into ischemia and remained elevated at 30 minutes into reperfusion, while phospho-p38 MAPK protein in the MPC group only increased significantly at 30 minutes into reperfusion.


CONCLUSIONS
The activation of p38 MAPK just acts as a mediator of MPC, whereas it acts as both a trigger and a mediator in IPC.
Zhang
Ye
Y
Department of Anesthesiology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. zhangye@mail.hf.ah.cn
Gu
Er-wei
EW
Zhang
Jian
J
Chen
Zhi-wu
ZW
D000818:Animals; D015153:Blotting, Western; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D019194:Ischemic Preconditioning; D020935:MAP Kinase Signaling System; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D007093:Imidazoles; D011725:Pyridines; D009020:Morphine; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580