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

Abstract

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 (B2 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 CHF 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<0.001 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.

Figure 1. Absolute changes in the FBF ratio between the infused and control arms in response to bradykinin

BK 30, FBF during the infusion of bradykinin at 30 pmol/min; BK 300, FBF during the infusion of bradykinin at 300 pmol/min. *P<0.05 (measured by using two-way ANOVA).

Figure 2. Changes in FVV as a percentage of the baseline in response to bradykinin

BK 30, FVV during the infusion of bradykinin at 30 pmol/min; BK 300, FVV during the infusion of bradykinin at 300 pmol/min. *P<0.05 (measured by using two-way ANOVA).

Figure 3. Percentage changes in the FBF ratio between the infused and control arms during infusion of bradykinin alone and co-infusion with B9340 or HOE140

BK 300, FBF during the infusion of bradykinin at 300 pmol/min. *P<0.05 (measured by using two-way ANCOVA).

Figure 4. Changes in FVV as a percentage of the baseline during infusion of bradykinin alone or co-infusion with B9340 or HOE140

BK 300, FVV during the infusion of bradykinin at 300 pmol/min. *P<0.05 (measured by using two-way ANCOVA).

Figure 5. Changes in FBF and FVV in healthy volunteers compared with ACEI-treated CHF patients and ARB-treated CHF patients.

(A) Percentage changes in the FBF ratio between the infused and control arms during infusion of B9340, after the period of normal saline washout. *P<0.05 (measure by paired Student's t test). (B) Changes in FVV as a percentage of the baseline during infusion of B9340 after the period of normal saline washout. *P<0.05 (measured by using a paired Student's t test). (C) Percentage change in FBF during infusion of B9340 or HOE140 in ACEI-treated CHF patients after the period of normal saline washout. *P<0.05 (measured by using a paired Student's t test). (D) Changes in FVV as a percentage of the baseline during infusion of B9340 or HOE140 in ACEI-treated CHF patients after the period of normal saline washout. P<0.05 (measured by using a paired Student's t test).