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

Gunaruwan P, Maher A, Williams L, Sharman J, Schmitt M, Campbell R, Frenneaux M - Clin. Sci. (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Medicine, Medical School, University of Birmingham, Edgbaston, UK. gunaruwan@doctors.org.uk

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.

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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).
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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).

Mentions: Infusion of B9340 or HOE140 did not reduce the FBF or unstressed FVV in healthy volunteers or in ARB-treated CHF patients (P>0.05, measured by using a paired t test; Figures 5A–5D). For HOE140 the percentage changes in FBF were −4.4±11.2 and 4.6±12.8%, and the percentage changes in unstressed FVV were −0.4±1.8% and −0.7±1.9% respectively (P>0.05, measured by using a paired t test) for normal healthy volunteers and for ARB-treated CHF patients; however, both B9340 and HOE140 reduced FBF and unstressed FVV in ACEI-treated CHF patients (P<0.05, measured by using a paired t test; Figures 5A–5D). For HOE140 the percentage change in FBF was −27.8±10.8% (P>0.05, measured by using a paired t test) and the percentage change in unstressed FVV was −4.0±1.8% (P>0.05, measured by using a paired t test) in ACEI-treated CHF patients.


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

Gunaruwan P, Maher A, Williams L, Sharman J, Schmitt M, Campbell R, Frenneaux M - Clin. Sci. (2009)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2636358&req=5

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).
Mentions: Infusion of B9340 or HOE140 did not reduce the FBF or unstressed FVV in healthy volunteers or in ARB-treated CHF patients (P>0.05, measured by using a paired t test; Figures 5A–5D). For HOE140 the percentage changes in FBF were −4.4±11.2 and 4.6±12.8%, and the percentage changes in unstressed FVV were −0.4±1.8% and −0.7±1.9% respectively (P>0.05, measured by using a paired t test) for normal healthy volunteers and for ARB-treated CHF patients; however, both B9340 and HOE140 reduced FBF and unstressed FVV in ACEI-treated CHF patients (P<0.05, measured by using a paired t test; Figures 5A–5D). For HOE140 the percentage change in FBF was −27.8±10.8% (P>0.05, measured by using a paired t test) and the percentage change in unstressed FVV was −4.0±1.8% (P>0.05, measured by using a paired t test) in ACEI-treated CHF patients.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Medicine, Medical School, University of Birmingham, Edgbaston, UK. gunaruwan@doctors.org.uk

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.

Show MeSH
Related in: MedlinePlus