Document Detail


Nitric oxide triggers delayed anesthetic preconditioning-induced cardiac protection via activation of nuclear factor-kappaB and upregulation of inducible nitric oxide synthase.
MedLine Citation:
PMID:  18708911     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Chen Hsiu Chen; Jiin Haur Chuang; Kang Liu; Julie Y H Chan
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  30     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-18     Completed Date:  2008-12-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  241-9     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Anesthetics, Inhalation / pharmacology
Animals
Gene Expression Regulation, Enzymologic
Heart / drug effects*
Ischemic Preconditioning, Myocardial
Isoflurane / pharmacology
Male
Myocardium / pathology*
NF-kappa B / metabolism*
Nitric Oxide Synthase Type II / biosynthesis*
Protein C / metabolism
Rats
Rats, Sprague-Dawley
Reperfusion Injury
Up-Regulation*
Chemical
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/NF-kappa B; 0/Protein C; 26675-46-7/Isoflurane; EC 1.14.13.39/Nitric Oxide Synthase Type II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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