Comparison of cardioprotective effects of mibefradil and ramipril in stroke-prone spontaneously hypertensive rats

• 来源期刊: 中国药理学报（英文版）
• 关键词: mibefradil ramipril angiotensin-converting enzyme inhibitors calcium channel blockers myocardial infarction heart failure cardiac remodeling ventricular function SHR-SP rats
• 年，卷（期）: 2004,（6）
• 页码范围: 763-768
• 页数: 6页
• 语种: 英文

摘要

AIM: To elucidate the cardioprotective effects of T-type calcium channel blocker mibefradil and compare with that of the angiotensin-converting enzyme inhibitor ramipril in a stroke-prone spontaneously hypertensive rats (SHRSP) model of congestive heart failure (CHF) after myocardial infarction (MI). METHODS: SHR-SP rats were subjected to permanent ligation of the left anterior decending coronary artery. Treatment with mibefradil (10after induction of MI. Sham-operated rats served as controls. RESULTS: In placebo-treated MI rats, six weeks after MI, left ventricular circumference, inner diameter, and left ventricular end-diastolic pressure (LVEDP) were increased, whereas mean arterial blood pressure (MAP) and maximum rate of rise of left ventricular pressure (dp/dtmax) were decreased compared with sham-operated controls (P＜0.01). In ramipril-treated MI rats, heart weight,heart weight to body weight ratio and interstitial collagen content were reduced (P＜0.05, P＜0.01), LVEDP was slightly decreased (P＞0.05), and dp/dtmax was improved (P＜0.01) compared with placebo-treated MI rats. In contrast, in mibefradil-treated MI rats, heart weight, heart weight to body weight ratio were slightly but not significantly reduced, LVEDP was slightly elevated compared with placebo-treated MI rats, and was elevated (P＜0.05)compared with ramipril-treated MI rats, although interstitial collagen content were reduced (P＜0.01) compared with placebo-treated MI rats. CONCLUSION: Chronic treatment with ramipril diminishes cardiac remodeling of heart failure after MI to a greater extent than mibefradil. Moreover, 6 weeks after MI, mibefradil treatment results in a slight rise in LVEDP compared with placebo-treated rats. Therefore, treatment with mibefradil might be deleterious rather than beneficial compared with ramipril or even placebo treatment in experimental MI.