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KMID : 0043320080310101257
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Archives of Pharmacal Research
2008 Volume.31 No. 10 p.1257 ~ p.1263
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The Mechanism of the Late Preconditioning Effect of 3-Nitropropionic Acid
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Basgut Bilgen
Caklcl And Iclal
Klllc Nedret
Akln K.Okhan
Basgut Ertug
Aypar Eda
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Abstract
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The aim of the present study was to investigate the mechanism of effect of 3-nitropropionic acid- (3-NP) induced late preconditioning in rat heart. For this purpose 20-30 min before 3-NP (20 mg/kg, i.p.) injection, the rats were treated intraperitoneally with 5-hydroxydecanoate (40 mg/kg, 5-HD, mitochondrial KATP-channel blocker), L-NAME (100 mg/kg, NOS inhibitor), N-2-mercaptopropionylglycine (100 mg/ kg , MPG, free radical scavenger), or superoxide dismutase+catalase (10000+10000 IU/kg , SOD+CAT). Control rats received saline only without 3-NP pretreatment. After two days, hearts were isolated and perfused at a constant pressure in a Langendorff apparatus. 15- min global ischemia followed by 30-min reperfusion was applied to all hearts. Pretreatment of 3-NP significantly reduced infarct size, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) levels, and incidence of ventricular tachycardia (VT) compared with the control group receiving saline only. 5-HD, L-NAME, MPG, or SOD+CAT treatment statistically reversed 3-NP-induced reduction in infarct size. Although CK-MB, LDH levels, and incidence of VT were also reduced by L-NAME, MPG, or SOD+CAT treatment, only 5-HD significantly inhibited beneficial effects of 3-NP on all of the parameters above. These results showed that mito-KATP channels play a pivotal role in late preconditioning effect of 3-NP in the isolated rat heart. However, other mediators such as reactive oxygen species and NO may be, at least in part, involved in mechanisms of this effect.
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KEYWORD
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3-Nitropropionic acid, Late preconditioning, Rat heart, Mito KATP channel, Free radicals
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