title: Cardioprotective effects of low-dose combination therapy with a statin and an angiotensin receptor blocker in a rat myocardial infarction model.
abstract: OBJECTIVE
  Statins attenuate angiotensin II-induced myocyte hypertrophy and this might increase the cardioprotective effects of renin-angiotensin system inhibition in the ischemic heart. In this study, we investigated the cardioprotective effects of combination therapy with low-dose simvastatin and low-dose losartan using a rat myocardial infarction model.
  
  
  METHODS
  Myocardial infarction was created in rats by left anterior descending artery ligation, and the animals were randomly allocated to one of four groups: control (n=8), losartan 3 mg/kg/day (n=8), simvastatin 2 mg/kg/day (n=8), and losartan 3 mg/kg/day plus simvastatin 2 mg/kg/day (n=8). Each treatment was started on the day of coronary ligation, and hemodynamics, myocardial blood flow, and infarct size were measured after 28 days.
  
  
  RESULTS
  Blood pressure, heart rate, and left ventricular systolic and end-diastolic pressures were not significantly different comparing the control group with the 3 other treatment groups. The peak positive first derivative of left ventricular pressure (peak LV dP/dt) was equivalent comparing the control group with the losartan and simvastatin groups. However, the peak LV dP/dt was greater in the losartan plus simvastatin group than in the control group (p<0.05). Myocardial blood flow, left ventricular weight, and infarct size were not significantly altered by the 3 treatments.
  
  
  CONCLUSIONS
  Treatment with 3 mg/kg/day losartan plus 2 mg/kg/day simvastatin but not losartan or simvastatin alone improved left ventricular systolic function in a rat myocardial infarction model. The result suggests that statins given in combination with angiotensin receptor blockers might have beneficial cardioprotective effects, even at low-doses for each agent.
authors.affiliation: Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Sohma
authors.forename: Teruo
authors.initials: T
authors.lastname: Inoue
authors.forename: Shichiro
authors.initials: S
authors.lastname: Abe
authors.forename: Isao
authors.initials: I
authors.lastname: Taguchi
authors.forename: Migaku
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Toyoda
authors.forename: Takuo
authors.initials: T
authors.lastname: Arikawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hikichi
authors.forename: Shoji
authors.initials: S
authors.lastname: Sanada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage
chemical_list: D057911:Angiotensin Receptor Antagonists; D002316:Cardiotonic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D019808:Losartan