TY - JOUR
T1 - Comparison of cardioprotective effects of mibefradil and ramipril in stroke-prone spontaneously hypertensive rats
AU - Xia, Qin-gui
AU - Reinecke, Alexander
AU - Dorenkamp, Marc
AU - Storz, Christain
AU - Bitterling, Havvo
AU - Penz, Susanne
AU - Cleutjens, Jack
AU - Daemen, Mat J. A. P.
AU - Simon, Reichiger
AU - Unger, Thomas
PY - 2004
Y1 - 2004
N2 - 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). 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. 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/dt(max)) 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/dt(max) 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. 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
AB - 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). 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. 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/dt(max)) 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/dt(max) 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. 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
M3 - Article
C2 - 15169629
SN - 1671-4083
VL - 25
SP - 763
EP - 768
JO - Acta Pharmacologica Sinica
JF - Acta Pharmacologica Sinica
IS - 6
ER -