Effects of bradykinin on venous capacitance in health and treated chronic heart failure

In the present study, we investigated the effects of basal and intra-arterial infusion of bradykinin on unstressed forearm vascular volume (a measure of venous tone) and blood flow in healthy volunteers (n = 20) and in chronic heart failure patients treated with ACEIs [ACE (angiotensin-converting enzyme) inhibitors] (n = 16) and ARBs (angiotensin receptor blockers) (n = 14). We used radionuclide plethysmography to examine the effects of bradykinin and of the bradykinin antagonists B9340 [B1 (type 1)/B2 (type 2) receptor antagonist] and HOE140 (132 antagonist). Bradykinin infusion increased unstressed forearm vascular volume in a similar dose-dependent manner in healthy volunteers and ARB-treated CHF patients (healthy volunteers maximum 12.3 +/- 2.1%, P < 0.001 compared with baseline; ARB-treated CHIP patients maximum 9.3 +/- 3.3%, P < 0.05 compared with baseline; P = not significant for difference between groups), but the increase in unstressed volume in ACEI-treated CHF patients was higher (maximum 28.8 +/- 7.8%, P < 0.00 1 compared with baseline; P < 0.05 for the difference between groups). In contrast, while the increase in blood flow in healthy volunteers (maximum 362 +/- 9%, P < 0.001) and in ACEI-treated CHF patients (maximum 376 +/- 12%, P < 0.001) was similar (P = not significant for the difference between groups), the increase in ARB-treated CHF patients was less (maximum 335 7%, P < 0.001; P < 0.05 for the difference between groups). Infusion of each receptor antagonist alone similarly reduced basal unstressed volume and blood flow in ACEI-treated CHF patients, but not in healthy volunteers or ARB-treated CHF patients. In conclusion, bradykinin does not contribute to basal venous tone in health, but in ACEI-treated chronic heart failure it does. In ARB-treated heart failure, venous responses to bradykinin are preserved but arterial responses are reduced compared with healthy controls. Bradykinin-mediated vascular responses in both health and heart failure are mediated by the B2, rather than the B1, receptor.