title: Renin-Angiotensin-Aldosterone Signaling Inhibitors-Losartan, Enalapril, and Cardosten-Prevent Infarction-induced Heart Failure Development in Rats.
abstract: BACKGROUND
  The activation of the renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of congestive heart failure, which is the reason that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin 2 receptor blockers (ARBs) have become established therapies for heart failure. However, it is still not known whether preventive treatment with losartan or enalapril can reduce symptoms of infarction-induced heart failure. Ultra-low dose (ULD) drug therapy is thought to exert specific activity, with a lower chance of side effects. OBJECTIVES • The research team had hypothesized that preventive treatment with inhibitors of RAAS signaling-losartan, enalapril, and a preparation of a ULD antibody (ie, cardosten), which target the angiotensin type 1 (AT1) receptor-might alleviate pathological hypertrophy and/or functional decline in infarction-induced heart failure.
  
  
  METHODS
  The research team treated male Wistar rats orally for 30 d with 20 mg/kg of losartan, 10 mg/kg enalapril, 5 or 7.5 mL/kg of cardosten, or a control solution, started 1 d prior to permanent coronary occlusion. A sham-operated group functioned as a second control group.
  
  
  METHODS
  The study was conducted at the Department of Biochemistry of the Faculty of Medicine at the University of Szeged in Szeged, Hungary, in cooperation with the Pharmahungary Group, also in Szeged, Hungary, and with OOO "NPF" Materia Medica Holding Ltd in Moscow, Russia.
  
  
  METHODS
  To determine cardiac functional parameters in vivo, the research team inserted a catheter into the left ventricle of the rats and measured the parameters of ventricular pressure, and cardiac output was determined by thermodilution. Morphological parameters were measured after heart isolation in transverse sections by a digital caliper.
  
  
  RESULTS
  A total of 30 d after permanent coronary ligation, both losartan and enalapril, significantly decreased mean arterial blood pressure (MABP), attenuated the development of the left-ventricular anterior-wall and septum hypertrophy, and reduced scar thickness compared with the vehicle control group. The deterioration of cardiac output and the increase in total peripheral resistance (TPR) due to coronary ligation were significantly inhibited by both losartan and enalapril. The effects of cardosten were comparable with those of losartan and enalapril on cardiac morphology, left ventricular function, and TPR; however, it did not influence MABP. Moreover, in contrast to losartan and enalapril, cardosten did not decrease the rate of survival.
  
  
  CONCLUSIONS
  The study was the first to have demonstrated that preventive treatment with losartan, enalapril, or cardosten can attenuate pathological hypertrophy in infarction-induced heart failure in rats.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kiss
authors.forename: Veronika
authors.initials: V
authors.lastname: Fekete
authors.forename: János
authors.initials: J
authors.lastname: Pálóczi
authors.forename: Márta
authors.initials: M
authors.lastname: Sárközy
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Murlasits
authors.forename: Judit
authors.initials: J
authors.lastname: Pipis
authors.forename: Irina A
authors.initials: IA
authors.lastname: Kheyfets
authors.forename: Julia L
authors.initials: JL
authors.lastname: Dugina
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Sergeeva
authors.forename: Oleg I
authors.initials: OI
authors.lastname: Epstein
authors.forename: Csaba
authors.initials: C
authors.lastname: Csonka
authors.forename: Tamás
authors.initials: T
authors.lastname: Csont
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.forename: Péter
authors.initials: P
authors.lastname: Bencsik
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000517:prevention & control; D006334:Heart Function Tests; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D019808:Losartan