Nitric oxide opens second window of protection in ischemic preconditioning via induction of heat-shock protein 72.
OBJECTIVE
To examine the inhibition of nitric oxide (NO) synthesis during ischemic preconditioning (IP) upon the induction of heat-shock protein 72 (HSP72) and the size-limiting effect of the second window of protection on infarction.


METHODS
Rabbits were subjected to either 4 cycles of 5-min long coronary artery occlusion separated by 10 min of reperfusion, or a sham operation. During this procedure, we administered 10 mg/kg of N(G)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) intravenously 5 min before IP followed by its continuous infusion (1.5 mg/kg/min). Twenty-four hours after IP or the sham operation, the hearts were rapidly excised for assay of HSP72 expression or were subjected to 30 min of coronary artery occlusion followed by 120 min of reperfusion, at which point infarct size (IS) was measured.


RESULTS
Twenty-four hours after IP or the sham operation, there was no difference in heart rate or mean arterial pressure between the groups. Immunoblotting revealed an increase in HSP72 protein levels in the IP group, which was blocked by L-NAME. IS in the IP rabbits was reduced compared with controls (29.8 +/- 3.7% vs. 50.8 +/- 4.3%, P < 0.01). IS in the IP rabbits was elevated as a result of L-NAME treatment (46.0 +/- 5.1%). Administration of L-arginine reversed the effects of L-NAME on the induction of HSP72 and IS (33.5 +/- 4.0%). The intravenous administration of S-nitroso-N-acetylpenicillamine (an NO donor, 15 microg/kg/min) over 20 min increased the induction of HSP72 and reduced IS (31.3 +/- 5.7%, P < 0.01 vs. control) 24 h later.


CONCLUSIONS
These findings suggest that NO may be involved in the induction of HSP72 and the opening of the second window of protection of IP.
Li
Weijie
W
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. weijie-li@163.net
Jia
Guoliang
G
Guo
Wenyi
W
Wang
Haichang
H
D000818:Animals; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D010396:Penicillamine