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


CONCLUSIONS
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.
Xia
Qin-Gui
QG
Department of Physiology, Wenzhou Medical College, Wenzhou 325027, China. xiaqingui@yahoo.com
Reinecke
Alexander
A
Dorenkamp
Marc
M
Storz
Christain
C
Bitterling
Havvo
H
Penz
Susanne
S
Cleutjens
Jack
J
Daemen
Mat Jap
MJ
Simon
Reichiger
R
Unger
Thomas
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006321:Heart / Q000033:anatomy & histology; D006339:Heart Rate / Q000187:drug effects; D020748:Mibefradil / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017725:Ventricular Pressure / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D020748:Mibefradil; D017257:Ramipril