title: Lipopolysaccharide triggers late preconditioning against myocardial infarction via inducible nitric oxide synthase.
abstract: OBJECTIVE
  The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) as a trigger in lipopolysaccharide (LPS)-induced late preconditioning against myocardial infarction.
  
  
  METHODS
  Rats were pretreated intraperitoneally with two different doses of LPS (0.5 or 2.5 mg/kg) or normal saline (control) 24 h prior to lethal myocardial ischemia. Subsequently, all rats were subjected to a sustained 30-min coronary occlusion followed by 180-min reperfusion. In the second study, total RNA and protein were extracted from myocardium of the control and LPS-treated rats (after 4, 6 and 24 h of treatment) for reverse transcription-polymerase chain reaction and Western blot analysis.
  
  
  RESULTS
  In LPS (2.5 mg/kg, but not 0.5 mg/kg)-treated rats receiving no pharmacological intervention, the percentage of myocardial infarct within the area at risk and left ventricle was significantly reduced to 42+/-4 and 24+/-2% (P<0.01) compared with the control group. The cardioprotection was abolished by injection of dexamethasone (4 mg/kg x 2, i.p.) or the selective iNOS inhibitor aminoguanidine (300 mg/kg x 2, s.c.) before LPS treatment. The expression of iNOS mRNA and the iNOS protein significantly increased 4 and 6 h after administration of LPS (2.5 mg/kg), respectively. The increases in iNOS mRNA and protein were eliminated by dexamethasone. But the iNOS mRNA and protein were not detectable 24 h after administration of LPS (2.5 mg/kg).
  
  
  CONCLUSIONS
  These data provide molecular and pharmacological evidence that LPS-induced late preconditioning against myocardial infarction is triggered by iNOS.
authors.affiliation: First Department of Surgery, Kagawa Medical University, 1750-1, Ikenobe, Miki, Kita, Kagawa, Japan. wang@kms.ac.jp
authors.forename: You-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Chubun
authors.initials: C
authors.lastname: Sato
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizoguchi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oe
authors.forename: Hajime
authors.initials: H
authors.lastname: Maeta
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D006146:Guanidines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine