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Chronic infusion of bradykinin delays the progression of heart failure and preserves vascular endothelium-mediated vasodilation in conscious dogs.

Tonduangu, Daniel; Hittinger, Luc; Ghaleh, Bijan; Le Corvoisier, Philippe; Sambin, Lucien; Champagne, Stéphane; Badoual, Thierry; Vincent, Fanny; Berdeaux, Alain; Crozatier, Bertrand; Su, Jin Bo.
Circulation; 109(1): 114-9, 2004 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-14662711

BACKGROUND:

This study examined the effects of chronic bradykinin infusion on hemodynamics and myocardial and endothelial functions during the development of heart failure.

METHODS AND 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.
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