Chronic infusion of bradykinin delays the progression of heart failure and preserves vascular endothelium-mediated vasodilation in conscious dogs.
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.
Tonduangu
Daniel
D
INSERM U400, Faculté de Médecine, Assistance Publique Hôpitaux de Paris, Créteil, France.
Hittinger
Luc
L
Ghaleh
Bijan
B
Le Corvoisier
Philippe
P
Sambin
Lucien
L
Champagne
Stéphane
S
Badoual
Thierry
T
Vincent
Fanny
F
Berdeaux
Alain
A
Crozatier
Bertrand
B
Su
Jin Bo
JB
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
D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin