Involvement of heme oxygenase-1 in delayed cardioprotection induced by monophosphoryl lipid A in rats.
OBJECTIVE
To explore whether the heme oxygenase-1 (HO-1) pathway is involved in the delayed cardioprotection induced by monophosphoryl lipid A (MLA).


METHODS
Sprague-Dawley rats were pretreated with MLA 24 h before the experiment. Ischemia-reperfusion injury was induced by 60 min coronary artery occlusion followed by 3 h reperfusion. Infarct size, the serum creatine kinase (CK) activity, the serum content of nitric oxide (NO), and expression of HO-1 mRNA and protein in the heart were measured.


RESULTS
Pretreatment with MLA (500 microg/kg, ip) markedly reduced infarct size and CK release and increased the serum content of NO (P < 0.01). The effects of MLA were completely abolished by pretreatment with L-nitroarginine methyl ester (L-NAME 10 mg/kg, ip), an inhibitor of NO synthase (P < 0.01), or Zinc protoporphyrin IX (45 micromol/kg, ip), an inhibitor of HO (P < 0.01). MLA caused a significant increase in the expression of HO-1 mRNA and protein, an effect which was not affected by L-NAME (P > 0.05).


CONCLUSIONS
The results suggest that the HO-1/NO pathway is involved in the delayed cardioprotection induced by MLA.
Ru
Rong
R
Department of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha 410078, China.
Peng
Jun
J
Ye
Feng
F
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003402:Creatine Kinase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051547:Heme Oxygenase-1; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D008050:Lipid A; D012333:RNA, Messenger; D009569:Nitric Oxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D003402:Creatine Kinase; C048436:monophosphoryl lipid A