The platelet activating factor triggers preconditioning-like cardioprotective effect via mitochondrial K-ATP channels and redox-sensible signaling.
Endogenous platelet activating factor (PAF) is involved in heart ischemic preconditioning. PAF can also afford pharmacological preconditioning. We studied whether mitochondrial-ATP-sensitive K(+) (mK(ATP)) channels and reactive oxygen species (ROS) are involved in PAF-induced cardioprotection. In Group 1 control hearts, Langendorff-perfused rat hearts underwent 30 min ischemia and 2 hours of reperfusion. Group 2 hearts, before ischemia, were perfused for 19 min with PAF (2x10(-11) M); Groups 3 and 4 hearts were co-infused with PAF and N-acetyl-L-cysteine or 5-hydroxydecanoate to scavenge ROS or to block mK(ATP) channels, respectively. Left ventricular pressure and infarct size were determined. PAF-pretreatment reduced infarct size (33 +/- 4% vs 64 +/- 4.6 % of the area at risk of control hearts) and improved pressure recovery. Infarct-sparing effect of PAF was abolished by N-acetyl-L-cysteine and 5-hydroxydecanoate. Thus, the cardioprotective effect exerted by PAF-pretreatment involves activation of mK(ATP) channels and redox signaling in pre-ischemic phase.
Penna
C
C
Laboratories of Physiology, Department of Clinical and Biological Sciences, University of Turin, Italy.
Mognetti
B
B
Tullio
F
F
Gattullo
D
D
Mancardi
D
D
Pagliaro
P
P
Alloatti
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury; D010084:Oxidation-Reduction / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D002316:Cardiotonic Agents; D010972:Platelet Activating Factor; D015221:Potassium Channels; D017382:Reactive Oxygen Species; C117780:mitochondrial K(ATP) channel