title: Comparison of cardioprotective effects of mibefradil and ramipril in stroke-prone spontaneously hypertensive rats.
abstract: 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.
authors.affiliation: Department of Physiology, Wenzhou Medical College, Wenzhou 325027, China. xiaqingui@yahoo.com
authors.forename: Qin-Gui
authors.initials: QG
authors.lastname: Xia
authors.forename: Alexander
authors.initials: A
authors.lastname: Reinecke
authors.forename: Marc
authors.initials: M
authors.lastname: Dorenkamp
authors.forename: Christain
authors.initials: C
authors.lastname: Storz
authors.forename: Havvo
authors.initials: H
authors.lastname: Bitterling
authors.forename: Susanne
authors.initials: S
authors.lastname: Penz
authors.forename: Jack
authors.initials: J
authors.lastname: Cleutjens
authors.forename: Mat Jap
authors.initials: MJ
authors.lastname: Daemen
authors.forename: Reichiger
authors.initials: R
authors.lastname: Simon
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
mesh_terms: 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*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D020748:Mibefradil; D017257:Ramipril