Effects of lercanidipine on coronary reactivity and myocardial remodeling in transition to heart failure in cardiomyopathic hamsters  

Lercanidipine对心肌病仓鼠心力衰竭过程中冠状反应和重构的作用(英文)

作　　者：MassicotteJ. LeonardiA. 等 

机构地区：[1]Départementdepharmacologie,facultédeMontréal,Montréal,QC,CanadaH3C3J7 [2]PharmaceuticalR&DDivision,RecordatiSpA,Milan,Italy

出　　处：《Acta Pharmacologica Sinica》2003年第3期199-206,共8页中国药理学报（英文版）

摘　　要：AIM: Lercanidipine is a new vasoselective dihydropyridine calcium channel blocker with a short plasma half-life, long duration of action, and demonstrated cardioprotective properties. We hypothesized that it might be effective at attenuating the adverse impact observed on the coronary compartment and myocardium in the transition phase to heart failure in the UM-X7.1 cardiomyopathic (CM) hamster. METHODS: The effects of 4-month exposure to lercanidipine 3 and 10 mg/kg (daily oral administration) were evaluated in 150-day-old CM hamsters and in age-matched normal hamsters. Coronary reactivity (reactive hyperemia to 30-s coronary occlusion) and the response to the administration of acetylcholine (100 nmol/L) and sodium nitroprusside (1 micromol/L) were assessed monthly, using the isolated perfused heart model. The left ventricular chamber dilatation index and wall thickness, myocardial fibrosis and myocardial capillary density (papillary muscle) were estimated in selected subgroups at monthly intervals. RESULTS: High-dose lercanidipine had beneficial effects on coronary dysfunctions: at month 4 of the treatment period, reactive hyperemia to short duration ischemia was improved, as was the endothelium-dependent vasodilator response (acetylcholine=68 %+/-16 % vs 11 %+/-5 % in untreated CM hamsters, P瞄准：Lercanidipine 是有短血浆半衰期，行动的长持续时间，和表明的 cardioprotective 性质的新 vasoselective dihydropyridine 钙隧道 blocker。我们假设了那它可能在不利影响在 UM-X7.1 cardiomyopathic (厘米) 在转变阶段在冠的分隔空间和心肌层上观察了到心失败的 attenuating 是有效的仓鼠。方法：到 lercanidipine 的 4 月的暴露的效果 3 和 10 mg/kg (每天口头的管理) 在 150-day-old 厘米仓鼠并且在匹配年龄的正常仓鼠被评估。冠的反应(反应 hyperemia 到 30-s 冠的吸藏) 并且对醋胆素(100 nmol/L ) 和钠 nitroprusside (1 micromol/L ) 的管理的反应每月被估计，用孤立的酒的心模型。左室的房间膨胀索引和墙厚度，心肌的纤维变性和心肌的毛状的密度(乳突的肌肉) 在每月的间隔在选择亚群被估计。结果：高剂量的 lercanidipine 在冠的机能障碍上有有益的效果：在月 4 处理时期点，，到短持续时间局部缺血的反应 hyperemia 被改进是内皮细胞层依赖者血管扩张药反应(在未经治疗的厘米仓鼠的 acetylcholine=68 %+/-16 % 对 11 %+/-5 % ，

关 键 词：Acetylcholine Animals Calcium Channel Blockers Capillaries Cardiomyopathies Cardiotonic Agents CRICETINAE DIHYDROPYRIDINES Female Heart Failure  Congestive Male MESOCRICETUS Myocardium NITROPRUSSIDE Research Support  Non-U.S. Gov't Vasodilator Agents Ventricular Remodeling 

分 类 号：R541.6[医药卫生—心血管疾病] R542.2[医药卫生—内科学]