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

作　　者：Qin-guiXIA AlexanderREINECKE MarcDORENKAMP ChristainSTORZ HavvoBITTERLING SusannePENZ JackCLEUTJENS MatJAPDAEMEN ReichigerSIMON ThomasLINGER 

机构地区：[1]DepartmentofPhysiology,WenzhouMedicalCollege,Wenzhou325027,China [2]ClinicofCardiology,UniversityofKiel,24105Kiel,Germany [3]InstituteofPharmacology,UniversityofKiel,24105Kiel,Germany [4]DepartmentofPathology,UniversityofMaastricht,Maastricht,TheNetherlands

出　　处：《Acta Pharmacologica Sinica》2004年第6期763-768,共6页中国药理学报（英文版）

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 (SHR- SP) 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 (10 mg·kg-1·d-1), ramipril (10 mg·kg-1·d-1), or placebo was initiated 4 weeks before surgery and continued up to 6 weeks after 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>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 signifi- cantly 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.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 (SHR- SP) 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 (10 mg·kg-1·d-1), ramipril (10 mg·kg-1·d-1), or placebo was initiated 4 weeks before surgery and continued up to 6 weeks after 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>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 signifi- cantly 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.

关 键 词：MIBEFRADIL RAMIPRIL angiotensin-converting enzyme inhibitors calcium channel blockers myocar-  dial infarction heart failure cardiac remodeling ventricular function SHR-SP rats 

分 类 号：R544.1[医药卫生—心血管疾病]