PMID- 18708911
OWN - NLM
STAT- MEDLINE
DCOM- 20081209
LR  - 20131121
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Linking)
VI  - 30
IP  - 3
DP  - 2008 Sep
TI  - Nitric oxide triggers delayed anesthetic preconditioning-induced cardiac 
      protection via activation of nuclear factor-kappaB and upregulation of inducible 
      nitric oxide synthase.
PG  - 241-9
LID - 10.1097/SHK.0b013e318162ad19 [doi]
AB  - Nitric oxide (NO) plays a pivotal role both in triggering and mediating delayed 
      protection against myocardial I/R injury during anesthetic-induced 
      preconditioning (APC). However, the signaling mechanisms that underlie this 
      phenomenon remain unclear. Using isoflurane as a representative anesthetic, the 
      present study tested the hypothesis that NO released after anesthetic-induced 
      preconditioning initiates delayed cardioprotection via activation of nuclear 
      transcription factor-kappaB (NF-kappaB), leading to myocardial adaptation by 
      upregulation of iNOS and increase in production of NO. Sprague-Dawley rats that 
      received open-chest surgery under pentobarbital anesthesia were subject to 30 min 
      of left coronary artery occlusion, followed by 120 min of reperfusion. Exposure 
      to 60 min of 2.1% isoflurane inhalation with oxygen 24 h before ischemia 
      significantly reduced I/R-induced myocardial infarct size that was associated 
      with overexpression of iNOS protein and increased NO content in the heart. These 
      protective effects were abolished by pretreatment with a NOS inhibitor, 
      N-nitro-L-arginine methyl ester, an NF-kappaB blocker, diethyldithiocarbamate, 
      before isoflurane, or a selective iNOS inhibitor, S-methylisothiourea, before 
      left coronary artery occlusion. Isoflurane exposure also evoked a robust increase 
      in myocardial NO content, followed by nucleus-bound translocation of p65 or p50 
      subunit of NF-kappaB and increase in NF-kappaB DNA-binding activity in heart 
      tissues. These molecular events after isoflurane exposure were blocked by 
      pretreatment with N-nitro-L-arginine methyl ester. We conclude that NO generated 
      immediately after isoflurane exposure triggers downstream activation of 
      NF-kappaB, resulting in subsequent upregulation of iNOS expression and NO 
      synthesis that mediate APC-induced delayed cardioprotection.
FAU - Chen, Chen Hsiu
AU  - Chen CH
AD  - Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung, 
      Taiwan, Republic of China.
FAU - Chuang, Jiin Haur
AU  - Chuang JH
FAU - Liu, Kang
AU  - Liu K
FAU - Chan, Julie Y H
AU  - Chan JY
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (NF-kappa B)
RN  - 0 (Protein C)
RN  - CYS9AKD70P (Isoflurane)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Anesthetics, Inhalation/pharmacology
MH  - Animals
MH  - Gene Expression Regulation, Enzymologic
MH  - Heart/*drug effects
MH  - Ischemic Preconditioning, Myocardial
MH  - Isoflurane/pharmacology
MH  - Male
MH  - Myocardium/*pathology
MH  - NF-kappa B/*metabolism
MH  - Nitric Oxide Synthase Type II/*biosynthesis
MH  - Protein C/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury
MH  - *Up-Regulation
EDAT- 2008/08/19 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/08/19 09:00
PHST- 2008/08/19 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/08/19 09:00 [entrez]
AID - 00024382-200809000-00003 [pii]
AID - 10.1097/SHK.0b013e318162ad19 [doi]
PST - ppublish
SO  - Shock. 2008 Sep;30(3):241-9. doi: 10.1097/SHK.0b013e318162ad19.