title: Chronic effects of early started angiotensin converting enzyme inhibition and angiotensin AT1-receptor subtype blockade in rats with myocardial infarction: role of bradykinin.
abstract: OBJECTIVE
  The long-term effects and mechanisms of early started angiotensin converting enzyme (ACE) inhibition post myocardial infarction (MI) are not well understood. Chronic effects of early ACE inhibition on hemodynamics, left ventricular diastolic wall stress and remodeling were, therefore, compared to that of angiotensin AT1-receptor subtype blockade in rats with experimental myocardial infarction. The contribution of bradykinin potentiation to both ACE inhibitor and angiotensin AT1-receptor subtype blockade was assessed by cotreatment of rats with a bradykinin B2-receptor antagonist.
  
  
  METHODS
  MI was produced by coronary artery ligation in adult male Wistar rats. The ACE inhibitor, quinapril (6 mg/kg per day), or the angiotensin AT1-receptor subtype blocker, losartan (10 mg/kg per day), administered by gavage, and the bradykinin B2-receptor antagonist, Hoe-140 (500 micrograms/kg per day s.c.), administered either alone or in combination with quinapril or losartan, were started 30 min after MI and continued for eight weeks.
  
  
  RESULTS
  Quinapril and losartan reduced left ventricular end-diastolic pressure and global left ventricular diastolic wall stress only in rats with large MI. Pressure volume curves showed a rightward shift in proportion to MI size that was not prevented by quinapril or losartan treatment. Only the ACE inhibitor reduced left ventricular weight and this effect was prevented by cotreatment with the bradykinin antagonist. Baseline and peak cardiac index and stroke volume index, as determined using an electromagnetic flowmeter before and after an acute intravenous volume load, were restored by quinapril, whereas losartan had no effects.
  
  
  CONCLUSIONS
  Treatments starting 30 min after coronary artery ligation, with either quinapril or losartan, reduced preload only in rats with large MI. Despite this unloading of the heart, structural dilatation was not prevented by this early treatment. Only quinapril improved cardiac performance and reduced left ventricular weight and this effect was abolished by cotreatment with Hoe-140, suggesting an angiotensin II blockade-independent, but bradykinin potentiation-dependent, mechanism.
authors.affiliation: II. Medizinische Klinik, Klinikum Mannheim, Universität Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Hu
authors.forename: P
authors.initials: P
authors.lastname: Gaudron
authors.forename: H J
authors.initials: HJ
authors.lastname: Anders
authors.forename: F
authors.initials: F
authors.lastname: Weidemann
authors.forename: O
authors.initials: O
authors.lastname: Turschner
authors.forename: M
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: G
authors.initials: G
authors.lastname: Ertl
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000803:Angiotensin I / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D007546:Isoquinolines / Q000627:therapeutic use*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D000077583:Quinapril; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C065679:icatibant; D000803:Angiotensin I; D019808:Losartan; D000077583:Quinapril; D001920:Bradykinin