Functional Effects of Endogenous Bradykinin in Congestive Heart Failure

Objectives. The purpose of this study was to determine the level and functional effects of endogenous bradykinin in congestive heart failure (CHF).

Background. There is experimental evidence that bradykinin is increased in several cardiac disease states. However, it is unknown whether plasma levels of bradykinin are elevated in CHF. Further, the cardiac and vascular responses to bradykinin in CHF are unclear.

Methods. The circulating levels of bradykinin and the effects of endogenous bradykinin were assessed in eight instrumented, conscious dogs both before and after pacing-induced CHF.

Results. Before CHF, the plasma bradykinin level was 53.1 ± 12.4 pg/ml. Blocking endogenous bradykinin with HOE-140 (0.3 mg/kg), a specific bradykinin B₂-receptor antagonist, produced no significant alterations in heart rate, left ventricular (LV) end-systolic pressure (P_es), total systemic resistance (TSR), the time constant of LV relaxation (tau) or the maximal rate of LV filling (dV/dt_max). However, coronary blood flow was significantly reduced (p < 0.05). LV contractile performance measured by the slopes of pressure–volume relations was unaffected. After induction of CHF, the plasma bradykinin level increased to 234.2 ± 19.4 pg/ml (p < 0.05). Blocking endogenous bradykinin with HOE-140 reduced coronary blood flow and produced significant increases in P_es and TSR, prolonged tau, decreased dV/dt_max and elevated minimal LV pressure and mean left atrial pressure. Furthermore, the slopes of pressure–volume relations (p < 0.05) were decreased, indicating depressed contractility with HOE-140 after CHF.

Conclusions. Before CHF, endogenous bradykinin results in coronary dilation but has no effect on systemic arterial vasodilation or cardiac performance. After CHF, endogenous bradykinin is significantly increased and, acting through B₂-receptors, produces coronary and arterial vasodilation and improves LV relaxation and contractile performance. Thus, endogenous bradykinin may play an important role in preserving cardiovascular function in CHF.