Delayed coronary endothelial protection 24 hours after preconditioning: role of free radicals.
BACKGROUND
Preconditioning (PC) induces delayed protection against myocardial ischemia/reperfusion (I/R) injury. Whether a similar late protective effect exists in coronary endothelial cells is not known. Thus, we assessed whether PC also induces late protection against endothelial injury after I/R and the potential role of reactive oxygen species as triggers for late PC in this setting.


RESULTS
Rats were subjected to sham surgery or to PC with 1 cycle of 2 minutes I/5 minutes R and 2 cycles of 5 minutes I/5 minutes R in the absence or presence of the free radical scavenger N-2-mercaptopropionyl glycine (MPG). Twenty-four hours later, rats were subjected to 20 minutes I/60 minutes R in the absence or presence of MPG. At the end of R, coronary segments (diameter, 200 to 300 microm) were removed distal to the site of occlusion and mounted in wire myographs. I/R reduced the relaxations to acetylcholine (maximal relaxations: sham, 72+/-6%; I/R, 31+/-6%), and this impairment was prevented by MPG (64+/-7%). PC improved the response to acetylcholine (48+/-6%), but this beneficial effect was abolished by MPG (23+/-5%).


CONCLUSIONS
PC induces late protection against reperfusion-induced coronary endothelial injury. Moreover, in addition to being mediators of endothelial injury during reperfusion after prolonged ischemia, reactive oxygen species produced during PC also protect the coronary endothelium from reperfusion injury 24 hours later.
Kaeffer
N
N
Department of Pharmacology, Vacomed, Rouen University School of Medicine and Rouen Hospital, France.
Richard
V
V
Thuillez
C
C
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D016166:Free Radical Scavengers; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013997:Time Factors; D008625:Tiopronin / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D012701:Serotonin; C002385:linsidomine; D008625:Tiopronin; D008981:Molsidomine; D000109:Acetylcholine