2000 Fiscal Year Final Research Report Summary
Crosstalk in the mechanism of preconditioning (Co-relation between the signal transductions and infarct-reducing effects)
| Project/Area Number |
11670667
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | GIFU UNIVERSITY |
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Principal Investigator |
UNO Yoshihiro Gifu University Hospital, Assistant Professor, 医学部・附属病院, 講師 (70293553)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Hisayoshi Gifu University, Professor, 医学部, 教授 (80115930)
MINATOGUCHI Shinya Gifu University, Associate Professor, 医学部, 助教授 (20190697)
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| Project Period (FY) |
1999 – 2000
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| Keywords | ischemic preconditioning / cross-talk / microdialysis / noradrenaline / adenosine / Protein kinase C / α1B adrenoceptor |
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| Research Abstract |
Background : Adenosine, noradrenaline and activation of protein kinase C (PKC) are thought to be mediators of ischemic preconditioning (PC). However, it is not clear whether these are cross-talking each other. Therefore, the aim of this study was to investigate the modulation of cardiac interstitial noradrenaline levels during PC by adenosine receptors and PKC, and to examine their relationship between noradrenaline and infarct reducing effect of PC.
Methods and Results : In Japanese white rabbits, myocardial interstitial noradrenaline levels were measured using a microdialysts technique. PC was elicited by a single episode of 5-min ischemia and 5-min reperfusion. Infarct size was measured in rabbits subjected to 30-min ischemia and 48-hour reperfusion. Tyramine or R-PIA (selective A1 agonist) was administered before 30-min ischemia in the absence or presence of 8SPT (non-selective adenosine blocker) and staurosporine, respectively.
1) In the PC groups, chloroethylchlonidine (CEC, α1B-blocker), CEC+R-PIA, CEC+CGS (adenosine A2 agonist), 8SPT, DPCPX (adenosine A1 blocker), DMPX (adenosine A2 blocker), 8SPT+tyramine or placebo saline was injected before and during PC.The PC significantly elevated the interstitial noradrenaline levels, which was blocked by PKC inhibitor staurosporine.
2) Both tyramine and R-PIA reduced the infarct size, which was blocked by CEC, 8SPT and DMPX.
3) The blocking effect of CEC on infarct size was completely abolished by adding R-PIA but not CGS.
4) The blocking effect of 8SPT on infarct size was completely abolished by adding tyramine.
Conclusions : It is concluded that PC elevates the interstitial noradrenaline level via activation of adenosine A2 receptors and/or PKC in sympathetic nerves, which contributes to the PC effect on infarct size.
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Research Products
(2 results)
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[Publications] Hashimoto K,Minatoguchi S,Hashimoto Y,,Uno Y,Arai M,Takemura G,Fujiwara T,Fujiwara H, et al.: "Role Of Protein Kinase C, KATP Channels And Dna Fragmentation In The Infarct Size-Reducing Effects Of The Free Radical Scavenger T-0970."Clinical and Experimental Pharmacology and Physiology. Mar5;28(3). 193-199 (2001)
Description
「研究成果報告書概要(和文)」より
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