| Leukotrienes(LTs) are potent eicosaniod lipid mediators derived from phospholipase -released fatty acid arachidonate. LTs are involved in numerous homestatic biological functions and inflammation. They are produced by the activation of 5-lipoxygenase(5-LO). Cysteinyl leukotrienes (Cys-LTs),including LTC4, D4and ? , are generated and released during myocardial infarction and ischaemic injury. The coronary vasculature, neutrophiles , monocytes, macrophages and mast cells are capable of generating LTs. Previous studies indicate that Cys-LTs possess a profile in cardiac, hemodynamic, and microcirculatory pathophysiology . Cys-LTs are important inflammatory mediators. They have potent constrictor actions on the microvasculature ; they can enhance vascular permeability ; they can cause coronary spasm; they also reduce myocardial contractility and cardiac output. The biological activities of LTs make it well suited for a role in the mediation of deleterious myocardial, vascular and microcirculatory effects in myocardial ischaemia.The prime mode of LTs action is through specific G protein-coupled receptors, which have been cloned recently. Thus enabling specific receptor antagonist development. The biosynthesis and actions are blocked by clinically relevant nonsteroidal anti-inflammatory drugs-leukotrienes modifiers. It was reported that5-lipoxygenase inhibitor BAY x1005 , could minimize the myocardial infarction size and reduce the mortality rate . Selective LTs receptor antagonists have been reported to reduce infarct size in the dog as well as protect ischaemia-reperfusion injury and post-ischaemic ventricular dysfunction in cats.Montelukast, {R- (E)}-1-{1-{3-{2- (7-chloro-2-quinolinyl) ethenyl} phenyl }-3-{ 2-( 1-hydroxy-1-methylethyl )phenyl }thio}methyl}cyclopropaneacetic acid, monosodium salt, is a potent antagonist of LTs (LTD4) which possesses anti-inflammatory and anti-asthma effects, and now is clinically used for treatment of bronchial asthma as a therapeutic drug named Singulair. It dramatically inhibited the plasma exudation induced by LTs, antigen and other stimuli in the airway, heart, skin and nose of guinea pigs and rats. However, the role of montelukast in the pathophysiology in myocardial ischemia has not been well explored. In this study, we made an experimental model of myocardial damage induced by isoproterenol injection in order to determine whether montelukast has significant beneficial effects in the cardiovascular system .We also investigate the characteristics of NF- K B and the changes of NOSs , ICAM-1 to gain insights into the mechanisms involved in the cardioprotective effect of montelukast.Methods 1. ChemicalsMontelukast was kindly gifted by Dr. John Obenchain (Merck Research Laboratories, New Jersey, USA); Dexamethasone was purchased from HengRui Pharmaceutical Corp.(NanJing, China); Isoproterenol(ISO)was obtained from Harvest Pharmaceutical Corp.(ShangHai, China);three subtypes of rabbit-anti-rat nitric oxide synthase(neuronal,inducible,endothelial NOS)antibodys, anti-rat-NF K B p65antibody, 3,3'-diaminobensidine tetrahydrochloride(DAB), streptavidivn-biotincornplex(SABC) kit were purchased from Boster Biological Technology LTD.(WuHan, China),anti-mouse-I K B a antibody was from ZhongShan Biological Technology Corp.(BeiJing, China). Nitric oxide and malondialdehyde(MDA) contend assay kit were purchased from JianChen Biological Technology LTD.(NanJing,China). Other chemicals were of analytical grade.2. Animal grouping and drugs administrationAdult male or female Sprague-Dawley rats (180 -250 g body weight ) were randomized into 6 groups:①control group; ②Iso group; ③Mon 3 group; ④ Mon 10 group; ⑤ Mon 30 group; ?Dex group. Normal rats in control group without any treatment. The rats in all the other five groups: were sc Iso ( isoproterenol , 2 mg.kg-1.d-1) at d3 and d4. The rats in Mon 3, Mon 10 and Mon30 group were ig montealukast 3, 10 and 30 mg.kg-1.d-1 respectively from d1 to d4; rats in the Dex group were ip dexamethason 2 mg.kg-1.d-1 at d3 and...
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