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通过超声心动图评估坎地沙坦和西拉普利对心肌梗死大鼠的影响。

Effects of candesartan and cilazapril on rats with myocardial infarction assessed by echocardiography.

作者信息

Yoshiyama M, Takeuchi K, Omura T, Kim S, Yamagishi H, Toda I, Teragaki M, Akioka K, Iwao H, Yoshikawa J

机构信息

First Department of Internal Medicine, and Pharmacology, Osaka City University Medical School, Osaka, Japan.

出版信息

Hypertension. 1999 Apr;33(4):961-8. doi: 10.1161/01.hyp.33.4.961.

Abstract

The purpose of this study was to compare the angiotensin II type 1 receptor antagonist candesartan cilexitil (candesartan) and the angiotensin-converting enzyme inhibitor cilazapril on cardiac function, assessed by Doppler echocardiography and cardiac gene expression associated with cardiac remodeling, in rats with myocardial infarction. Candesartan or cilazapril was administered after myocardial infarction. At 1 and 4 weeks after myocardial infarction, cardiac function and mRNA expression in noninfarcted myocardium were analyzed. Candesartan and cilazapril equally prevented increases in hypertrophy in noninfarcted myocardium, left ventricular dilatation, and ejection fraction at 4 weeks. The E-wave/A-wave velocity ratio and the rate of E-wave deceleration, measures of diastolic function, increased to 9.2+/-0.6 and 26.3+/-2. 6 m/s2 at 1 week after myocardial infarction. Candesartan and cilazapril, administered at a dose of 1 mg/kg per day, prevented increases in E-wave/A-wave velocity ratio and E-wave deceleration at 1 and 4 weeks. Candesartan and cilazapril significantly suppressed increased mRNA expression of beta-myosin heavy chain, alpha-skeletal actin, and atrial natriuretic peptide in noninfarcted ventricle at 1 and 4 weeks and expression of collagen I and III at 4 weeks to a similar extent. When given at a dose of 10 mg/kg per day, both candesartan and cilazapril prevented cardiac dysfunction and gene expression to the same extent as when given at 1 mg/kg per day. In conclusion, Doppler echocardiography showed that candesartan and cilazapril equally improved systolic and diastolic function and that ventricular remodeling accompanied modulation of cardiac gene expression.

摘要

本研究旨在比较血管紧张素II 1型受体拮抗剂坎地沙坦西酯(坎地沙坦)和血管紧张素转换酶抑制剂西拉普利对心肌梗死大鼠心脏功能的影响,采用多普勒超声心动图评估心脏功能,并检测与心脏重塑相关的心脏基因表达。心肌梗死后给予坎地沙坦或西拉普利。在心肌梗死后1周和4周,分析非梗死心肌的心脏功能和mRNA表达。坎地沙坦和西拉普利同样能在4周时防止非梗死心肌肥厚增加、左心室扩张和射血分数增加。舒张功能指标E波/A波速度比值和E波减速速率在心肌梗死后1周时分别增加到9.2±0.6和26.3±2.6 m/s²。每天给予1 mg/kg剂量的坎地沙坦和西拉普利可防止1周和4周时E波/A波速度比值和E波减速增加。坎地沙坦和西拉普利在1周和4周时显著抑制非梗死心室中β-肌球蛋白重链、α-骨骼肌肌动蛋白和心钠素mRNA表达增加,在4周时对I型和III型胶原表达的抑制程度相似。当每天给予10 mg/kg剂量时,坎地沙坦和西拉普利预防心脏功能障碍和基因表达的程度与每天给予1 mg/kg时相同。总之,多普勒超声心动图显示坎地沙坦和西拉普利同样能改善收缩和舒张功能,且心室重塑伴随着心脏基因表达的调节。

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