title: Chronic infusion of bradykinin delays the progression of heart failure and preserves vascular endothelium-mediated vasodilation in conscious dogs.
abstract: BACKGROUND
  This study examined the effects of chronic bradykinin infusion on hemodynamics and myocardial and endothelial functions during the development of heart failure.
  
  
  RESULTS
  Sixteen instrumented dogs were randomized to receive through the left atria either vehicle or bradykinin (1 microg/min) during ventricular pacing (250 bpm, 5 weeks). Hemodynamic and left ventricular (LV) parameters and the vasodilator responses to intravenous acetylcholine (0.3 to 3 microg/kg) and nitroglycerin (1 to 10 microg/kg) were examined in the control and after 3 and 5 weeks of pacing. The expression of endothelial NOS in femoral, carotid, and renal arteries was determined by Western blot analysis. After 3 weeks of pacing, changes in LV diastolic and systolic parameters were significantly lower in bradykinin-treated than vehicle-treated dogs (LV end-diastolic pressure, +10+/-3 versus +19+/-2 mm Hg; time constant of LV isovolumic relaxation, +11+/-2 versus +17+/-1 ms; LV wall thickening, -33+/-18% versus -75+/-9%; and cardiac output, -16+/-6% versus -32+/-6%; all P<0.05). Compared with vehicle-treated dogs, bradykinin-treated dogs had a reduced rightward shift of the diastolic LV pressure-diameter relation and a reduced diastolic LV wall stress. Similar trends were observed after 5 weeks. The vasodilator response to nitroglycerin was preserved in both groups. The response to acetylcholine was blunted in vehicle-treated but preserved in bradykinin-treated dogs. Vascular endothelial NOS expression decreased in vehicle-treated but was preserved in bradykinin-treated dogs.
  
  
  CONCLUSIONS
  In conscious dogs, chronic bradykinin infusion delays the heart failure progression by preserving LV diastolic and systolic functions and by preserving vascular endothelial function.
authors.affiliation: INSERM U400, Faculté de Médecine, Assistance Publique Hôpitaux de Paris, Créteil, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tonduangu
authors.forename: Luc
authors.initials: L
authors.lastname: Hittinger
authors.forename: Bijan
authors.initials: B
authors.lastname: Ghaleh
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Corvoisier
authors.forename: Lucien
authors.initials: L
authors.lastname: Sambin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Champagne
authors.forename: Thierry
authors.initials: T
authors.lastname: Badoual
authors.forename: Fanny
authors.initials: F
authors.lastname: Vincent
authors.forename: Alain
authors.initials: A
authors.lastname: Berdeaux
authors.forename: Bertrand
authors.initials: B
authors.lastname: Crozatier
authors.forename: Jin Bo
authors.initials: JB
authors.lastname: Su
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001920:Bradykinin / Q000494:pharmacology* / Q000627:therapeutic use; D002302:Cardiac Output / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D009200:Myocardial Contraction / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D005996:Nitroglycerin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin