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

Prasad Gunaruwan, Abdul Maher, L. Williams, James Sharman, Matthias Schmitt, Ross Campbell, Michael Frenneaux

Research output: Contribution to journalArticle

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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 (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.

Original languageEnglish
Pages (from-to)443-450
Number of pages8
JournalClinical Science
Volume116
Issue number5-6
DOIs
Publication statusPublished - 1 Mar 2009

Keywords

  • angiotensin-converting enzyme inhibitor (ACEI)
  • angiotensin receptor blocker (ARB)
  • bradykinin
  • bradykinin receptor
  • heart failure
  • venous capacitance
  • converting enzyme-inhibitors
  • coronary-artery-disease
  • endothelial dysfunction
  • kinin receptors
  • human forearm
  • aspirin
  • trial
  • tone
  • vasodilation
  • vasculature

Cite this

Gunaruwan, P., Maher, A., Williams, L., Sharman, J., Schmitt, M., Campbell, R., & Frenneaux, M. (2009). Effects of bradykinin on venous capacitance in health and treated chronic heart failure. Clinical Science, 116(5-6), 443-450. https://doi.org/10.1042/CS20080096

Effects of bradykinin on venous capacitance in health and treated chronic heart failure. / Gunaruwan, Prasad; Maher, Abdul; Williams, L.; Sharman, James; Schmitt, Matthias; Campbell, Ross; Frenneaux, Michael.

In: Clinical Science, Vol. 116, No. 5-6, 01.03.2009, p. 443-450.

Research output: Contribution to journalArticle

Gunaruwan, P, Maher, A, Williams, L, Sharman, J, Schmitt, M, Campbell, R & Frenneaux, M 2009, 'Effects of bradykinin on venous capacitance in health and treated chronic heart failure', Clinical Science, vol. 116, no. 5-6, pp. 443-450. https://doi.org/10.1042/CS20080096
Gunaruwan P, Maher A, Williams L, Sharman J, Schmitt M, Campbell R et al. Effects of bradykinin on venous capacitance in health and treated chronic heart failure. Clinical Science. 2009 Mar 1;116(5-6):443-450. https://doi.org/10.1042/CS20080096
Gunaruwan, Prasad ; Maher, Abdul ; Williams, L. ; Sharman, James ; Schmitt, Matthias ; Campbell, Ross ; Frenneaux, Michael. / Effects of bradykinin on venous capacitance in health and treated chronic heart failure. In: Clinical Science. 2009 ; Vol. 116, No. 5-6. pp. 443-450.
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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 (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.",
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N2 - 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.

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KW - heart failure

KW - venous capacitance

KW - converting enzyme-inhibitors

KW - coronary-artery-disease

KW - endothelial dysfunction

KW - kinin receptors

KW - human forearm

KW - aspirin

KW - trial

KW - tone

KW - vasodilation

KW - vasculature

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