FUNCTIONAL-EFFECTS OF ENDOGENOUS BRADYKININ IN CONGESTIVE-HEART-FAILURE

Objectives. The purpose of this study was to determine the level and f unctional 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 wh ether plasma levels of bradykinin are elevated in CHF, Further, the ca rdiac and vascular responses to bradykinin in CHF are unclear. Methods . The circulating levels of bradykinin and the effects of endogenous b radykinin were assessed in eight instrumented, conscious dogs both bef ore and after pacing induced CBF. Results. Before CHF, the plasma brad ykinin level was 53.1 +/- 12.4 pg/ml. Blocking endogenous bradykinin w ith HOE-140 (0.3 mg/kg), a specific bradykinin B-2-receptor antagonist , produced no significant alterations in heart rate, left ventricular (LV) end-systolic pressure (P-es), total systemic resistance (TSR), th e time constant of LV relaxation (tau) or the maximal rate of LV filli ng (dV/dt(max)). However, coronary blood flow was significantly reduce d (p < 0.05). LV contractile performance measured by the slopes of pre ssure-volume relations was unaffected. After induction of CHF, the pla sma bradykinin level increased to 234.2 +/- 19.4 pg/ml (p < 0.05). Blo cking endogenous bradykinin with HOE-140 reduced coronary blood how an d produced significant increases in P-es and TSR, prolonged tau, decre ased 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 af ter CHF. Conclusions. Before CHF, endogenous bradykinin results in cor onary dilation but has no effect on systemic arterial vasodilation or cardiac performance. After CHF, endogenous bradykinin is significantly increased and, acting through B-2-receptors, produces coronary and ar terial vasodilation and improves LV relaxation and contractile perform ance. Thus, endogenous bradykinin may play an important role in preser ving cardiovascular function in CHF. (C) 1998 by the American College of Cardiology.