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

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