title: The mechanism of the late preconditioning effect of 3-nitropropionic acid.
abstract: 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 K(ATP)-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-K(ATP) 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.
authors.affiliation: Gazi University, Faculty of Pharmacy, Department of Pharmacology, Etiler, Ankara, Turkey. bilgenbasgut@gmail.com
authors.forename: Bilgen
authors.initials: B
authors.lastname: Basgut
authors.forename: Eda
authors.initials: E
authors.lastname: Aypar
authors.forename: Ertug
authors.initials: E
authors.lastname: Basgut
authors.forename: K Okhan
authors.initials: KO
authors.lastname: Akin
authors.forename: Nedret
authors.initials: N
authors.lastname: Kilic
authors.forename: Iclal
authors.initials: I
authors.lastname: Cakici
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D054086:KATP Channels / Q000819:agonists / Q000037:antagonists & inhibitors; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D009574:Nitro Compounds / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D005609:Free Radicals; D054086:KATP Channels; D009574:Nitro Compounds; D026902:Potassium Channel Blockers; D011422:Propionates; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D052250:Nitric Oxide Synthase Type III; D052279:Creatine Kinase, MB Form; C015392:3-nitropropionic acid; D019331:NG-Nitroarginine Methyl Ester