title: Investigations on the role of leukotrienes in remote hind limb preconditioning-induced cardioprotection in rats.
abstract: The cardioprotective effects of remote hind limb preconditioning (RIPC) are well established, but its mechanisms still remain to be explored. Therefore, the present study was aimed to explore the possible involvement of 5-lipoxygenase-derived leukotrienes in RIPC. The hind limb was tied by a pressure cuff and was subjected to four episodes of inflation and deflation (5min each) to induce remote hind-limb preconditioning. Thereafter, the hearts were isolated and were subjected to global ischemia (30min) followed by reperfusion (120min) on the Langendorff apparatus. The extent of myocardial injury was assessed by measuring lactate dehydrogenase (LDH) and creatine kinase (CK) levels in the coronary effluent; the infarct size using TTC staining, and the hemodynamic parameters including LVDP, dp/dtmax and dp/dtmin. RIPC significantly decreased ischemia and reperfusion-induced increase in LDH, CK release, infarct size and improved LVDP, dp/dtmax and dp/dtmin. Administration of montelukast, leukotriene receptor antagonist (10 and 20mg/kg) and zileuton, 5-lipoxygenase inhibitor, (2.5 and 5mg/kg) abolished RIPC-induced cardioprotection. It may be concluded that hind limb ischemia stimulates 5-lipoxygenase to release leukotrienes which may elicit cardioprotection by humoral or neurogenic pathway.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
authors.forename: Baljeet
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
authors.forename: Puneet Kaur
authors.initials: PK
authors.lastname: Randhawa
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India. Electronic address: amteshwarjaggi@yahoo.co.in.
authors.forename: Amteshwar Singh
authors.initials: AS
authors.lastname: Jaggi
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020024:Leukotriene Antagonists / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D007770:L-Lactate Dehydrogenase; D001094:Arachidonate 5-Lipoxygenase; D003402:Creatine Kinase
keywords: Cardioprotection; Leukotrienes; Montelukast; Remote hind limb preconditioning; Zileuton