title: Effects of the vasopeptidase inhibitor omapatrilat on peri- and postmyocardial infarction in Zucker lean rats.
abstract: BACKGROUND
  The vasopeptidase inhibitor omapatrilat improves insulin sensitivity and survival following myocardial infarction (MI). It also improves left ventricular (LV) remodelling following MI and reduces MI size.
  
  
  OBJECTIVE
  To determine whether improvement in LV remodelling and function is accompanied by a reduction in fetal gene expression of the contractile apparatus, and whether reduction in MI size is accompanied by an increase in the expression of the glucose transporter GLUT-4.
  
  
  METHODS
  Eighty-nine rats were pretreated for seven days with omapatrilat 20 mg/kg/day and 91 rats were left untreated. MI was induced in 180 Zucker lean male rats by ligating the left anterior descending coronary artery, and omapatrilat was given for another 38 days in the survivors. After 30 days, echocardiography was performed. At 38 days, hemodynamic measurements were performed, the rats were sacrificed and morphological measurements were done. Using quantitative reverse transcriptase-polymerase chain reaction, gene expression was measured in the LV using transcript levels.
  
  
  RESULTS
  Treatment with omapatrilat resulted in improved early (24 h) and late (38 days) survival following MI (50% to 67%, P=0.023, and 44% to 59%, P=0.045, respectively). Omapatrilat treatment reduced MI size and resulted in beneficial ventricular remodelling as reflected by a reduction in cardiac dimensions by echocardiography, and LV and right ventricular hypertrophy, which resulted in borderline hemodynamic improvement. A large MI resulted in an increased expression of beta-myosin heavy chain, alpha-skeletal actin and atrial natriuretic peptide, and a decreased expression of GLUT-4. Omapatrilat treatment did not modify the expression of these genes.
  
  
  CONCLUSIONS
  The results suggest that the vasopeptidase inhibitor omapatrilat does not modify fetal gene expression of the contractile apparatus or the expression of GLUT-4 despite reducing cardiac hypertrophy and MI size.
authors.affiliation: University Health Network, Toronto General Hospital, Toronto, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lapointe
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Parker
authors.forename: Jim N
authors.initials: JN
authors.lastname: Tsoporis
authors.forename: Quang T
authors.initials: QT
authors.lastname: Nguyen
authors.forename: François
authors.initials: F
authors.lastname: Marcotte
authors.forename: Albert
authors.initials: A
authors.lastname: Adam
authors.forename: Ingo
authors.initials: I
authors.lastname: Lou
authors.forename: Jean-Lucien
authors.initials: JL
authors.lastname: Rouleau
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000187:drug effects; D051275:Glucose Transporter Type 4; D006352:Heart Ventricles / Q000737:chemistry; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology; D008026:Ligation; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D009124:Muscle Proteins / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013841:Thiazepines / Q000494:pharmacology / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects; D024723:Ventricular Myosins / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011480:Protease Inhibitors; D011725:Pyridines; C495694:Slc2a4 protein, rat; D013841:Thiazepines; C106266:omapatrilat; D009320:Atrial Natriuretic Factor; D024723:Ventricular Myosins