Differential activation of mitogen-activated protein kinases in ischemic and nitroglycerin-induced preconditioning.
Previous studies have shown that the cardioprotective effect of ischemic preconditioning (IPC) can be mimicked pharmacologically with clinically relevant agents, including nitric oxide (NO) donors. However, whether pharmacological preconditioning shares the same molecular mechanism with IPC is not fully elucidated. The present study aimed to determine the activation of mitogen-activated protein kinases (MAPKs) (ERK1/2, p38 MAPK and p46/p54 JNKs) during ischemia and at reperfusion in nitroglycerin-induced preconditioning as compared to IPC and to correlate this with the conferred cardioprotection in anesthetized rabbits. Sixty minutes of intravenous administration of nitroglycerin was capable of inducing both early and late phase preconditioning in anesthetized rabbits, as it was expressed by the reduction of infarct size. Despite the cardioprotective effect conferred by both ischemic and nitroglycerin-induced preconditioning, there was a differential phosphorylation of MAPKs between the studied groups. p38 MAPK was activated early in ischemia in both ischemic and the early nitroglycerin-induced preconditioning while JNKs were markedly increased only after IPC. Furthermore, in these groups, ERK1/2 were activated during reperfusion. A different profile was observed in the late preconditioning induced by nitroglycerin with increased p38 MAPK and ERK1/2 phosphorylation during late ischemia. No activation of JNKs was observed at any time point in this group. It seems that activation of individual MAPK subfamilies depends on the nature of preconditioning stimulus.
Iliodromitis
Efstathios K
EK
2nd University Department of Cardiology Medical School Attikon General Hospital, University of Athens, Athens, 12462, Greece.
Gaitanaki
Catherine
C
Lazou
Antigone
A
Aggeli
Ioanna-Katerina
IK
Gizas
Vassilios
V
Bofilis
Elias
E
Zoga
Anastasia
A
Beis
Isidoros
I
Kremastinos
Dimitrios Th
DT
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D005996:Nitroglycerin / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D014665:Vasodilator Agents; D020928:Mitogen-Activated Protein Kinases; D005996:Nitroglycerin