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The involvement of cytokines in the second window of ischaemic preconditioning
Author(s) -
Yamashita Nobushige,
Hoshida Shiro,
Otsu Kinya,
Taniguchi Naoyuki,
Kuzuya Tsunehiko,
Hori Masatsugu
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703594
Subject(s) - cardioprotection , ischemia , medicine , myocardial infarction , reperfusion injury , ischemic preconditioning , superoxide dismutase , pharmacology , chemistry , oxidative stress
We utilized a rat model of myocardial infarction to investigate whether manganese superoxide dismutase (Mn‐SOD), an intrinsic radical scavenger, and tumour necrosis factor‐ α (TNF‐α) and/or interleukin‐1β (IL‐1β) are involved in the late phase of ischaemic preconditioning (IP). IP was induced in anaesthetized rats by four 3‐min left coronary artery (LCA) occlusions, each separated by 10 min of reperfusion. Twenty‐four hours after the repetitive brief ischaemia, the LCA was occluded for 20 min followed by reperfusion for 48 h. IP reduced the infarct size by approximately 46% as determined after 48 h of reperfusion. Antisense oligodeoxynucleotides to Mn‐SOD inhibited the increases in Mn‐SOD content and activity, and abolished the expected decrease in myocardial infarct size. Sense or scrambled oligodeoxynucleotides did not abolish either Mn‐SOD induction or tolerance to ischaemia/reperfusion. The simultaneous administration of the antibodies to TNF‐α (0.5 ml) and IL‐1β (0.5 mg) prior to IP abolished the cardioprotection and the increase in Mn‐SOD activity induced by IP. We conclude that the induction and activation of Mn‐SOD, mediated by TNF‐α and IL‐1β after IP, plays an important role in the acquisition of late‐phase cardioprotection against ischaemia/reperfusion injury in rats.British Journal of Pharmacology (2000) 131 , 415–422; doi: 10.1038/sj.bjp.0703594