Nitric oxide induces heat shock protein 72 production and delayed protection against myocardial ischemia in rabbits via activating protein kinase C.
BACKGROUND
Nitric oxide (NO) is a biologically active molecule which has been reported to protect the heart against ischemia and reperfusion injury in different species. This study aimed to test the hypothesis that nitric oxide may induce the expression of heat shock protein 72 (HSP72) which may protect the heart against ischemia.


METHODS
Rabbits were given intravenous saline or S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, or Zaprinast, an inhibitor of cyclic guanosine monophosphate (GMP)-phosphodiesterase, which may increase myocardial cyclic GMP content. Twenty-four hours later, the rabbits were either sampled to measure HSP72, or induced with a 30-minute coronary occlusion followed by a 120-minute reperfusion, and then the infarct size was measured. Meanwhile, chelerythrine (CHE, an inhibitor of protein kinase C) was given intravenously 5 minutes before SNAP injection and the effect on HSP72 expression and infarct size was determined.


RESULTS
Twenty-four hours after pretreatment, immunoblotting showed HSP72 expression increased in the SNAP group compared with control groups, and this was blocked by CHE. Myocardial infarct size in the SNAP group was smaller than that of the control group ((32.4 +/- 5.8)% vs (51.1 +/- 4.7)%, P < 0.05). Pretreated with CHE abolished the infarct size-limiting effect of SNAP ((46.0 +/- 5.1)%). Pretreatment with Zaprinast neither induced HSP72 expression nor reduced infarct size ((55.4 +/- 5.4)%).


CONCLUSIONS
NO induced HSP72 expression and a delayed protection to the heart via the activities of protein kinase C by a cyclic GMP-independent pathway.
Li
Wei-jie
WJ
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710033, China. liweijie@fmmu.edu.cn
Zhao
Zhi-jing
ZJ
Liu
Bing
B
Zhang
Dian-xin
DX
Li
Fei
F
Wang
Hai-chang
HC
Guo
Wen-yi
WY
Jia
Guo-liang
GL
Kitakaze
Masafumi
M
Hori
Masatsugu
M
D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000096:biosynthesis*; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011688:Purinones / Q000494:pharmacology; D011817:Rabbits; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
D053119:Benzophenanthridines; D050884:HSP72 Heat-Shock Proteins; D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; C016299:chelerythrine; D011493:Protein Kinase C; C011145:zaprinast; D006152:Cyclic GMP