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Bradykinin contributes to the systemic hemodynamic effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure.
Arterioscler Thromb Vasc Biol. 2004 Jun; 24(6):1043-8.AT

Abstract

BACKGROUND

Bradykinin is an endogenous vasodilator that may contribute to the systemic effects of angiotensin-converting enzyme (ACE) inhibitor therapy. Using B9340, a bradykinin receptor antagonist, we determined the contribution of bradykinin to the systemic hemodynamic effects of long-term ACE inhibition in patients with chronic heart failure.

METHODS AND RESULTS

Fourteen patients with heart failure received enalapril (10 mg twice daily) or losartan (50 mg twice daily) in a randomized double-blind crossover trial. After 6 weeks treatment, patients underwent right heart catheterization and were randomized to an intravenous infusion of B9340 (2 to 20 microg/kg per minute) or saline placebo. After B9340 infusion in patients treated with enalapril, mean arterial pressure (+5.2 mm Hg), systemic vascular resistance (+315 dynes x s/cm5), pulmonary arterial wedge pressure (-1.4 mm Hg), and mean pulmonary arterial pressure (-1.3 mm Hg) were greater compared with losartan (P<0.005, P=0.07, P<0.0001, and P<0.05 respectively) or placebo infusion (P< or =0.005 for all). There was a reduction in cardiac output after B9340 with enalapril compared with placebo (P<0.001) but not losartan.

CONCLUSIONS

Bradykinin contributes to the systemic hemodynamic effects of long-term ACE inhibition in patients with heart failure. This mechanism may explain the apparent clinical differences between ACE inhibitors and angiotensin receptor blockers in the treatment of heart failure.

Authors+Show Affiliations

Centre for Cardiovascular Science, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom EH16 4SB. nick.cruden@ed.ac.uk.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15105283

Citation

Cruden, Nicholas L M., et al. "Bradykinin Contributes to the Systemic Hemodynamic Effects of Chronic Angiotensin-converting Enzyme Inhibition in Patients With Heart Failure." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 6, 2004, pp. 1043-8.
Cruden NL, Witherow FN, Webb DJ, et al. Bradykinin contributes to the systemic hemodynamic effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure. Arterioscler Thromb Vasc Biol. 2004;24(6):1043-8.
Cruden, N. L., Witherow, F. N., Webb, D. J., Fox, K. A., & Newby, D. E. (2004). Bradykinin contributes to the systemic hemodynamic effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure. Arteriosclerosis, Thrombosis, and Vascular Biology, 24(6), 1043-8.
Cruden NL, et al. Bradykinin Contributes to the Systemic Hemodynamic Effects of Chronic Angiotensin-converting Enzyme Inhibition in Patients With Heart Failure. Arterioscler Thromb Vasc Biol. 2004;24(6):1043-8. PubMed PMID: 15105283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bradykinin contributes to the systemic hemodynamic effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure. AU - Cruden,Nicholas L M, AU - Witherow,Fraser N, AU - Webb,David J, AU - Fox,Keith A A, AU - Newby,David E, Y1 - 2004/04/22/ PY - 2004/4/24/pubmed PY - 2004/11/9/medline PY - 2004/4/24/entrez SP - 1043 EP - 8 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 24 IS - 6 N2 - BACKGROUND: Bradykinin is an endogenous vasodilator that may contribute to the systemic effects of angiotensin-converting enzyme (ACE) inhibitor therapy. Using B9340, a bradykinin receptor antagonist, we determined the contribution of bradykinin to the systemic hemodynamic effects of long-term ACE inhibition in patients with chronic heart failure. METHODS AND RESULTS: Fourteen patients with heart failure received enalapril (10 mg twice daily) or losartan (50 mg twice daily) in a randomized double-blind crossover trial. After 6 weeks treatment, patients underwent right heart catheterization and were randomized to an intravenous infusion of B9340 (2 to 20 microg/kg per minute) or saline placebo. After B9340 infusion in patients treated with enalapril, mean arterial pressure (+5.2 mm Hg), systemic vascular resistance (+315 dynes x s/cm5), pulmonary arterial wedge pressure (-1.4 mm Hg), and mean pulmonary arterial pressure (-1.3 mm Hg) were greater compared with losartan (P<0.005, P=0.07, P<0.0001, and P<0.05 respectively) or placebo infusion (P< or =0.005 for all). There was a reduction in cardiac output after B9340 with enalapril compared with placebo (P<0.001) but not losartan. CONCLUSIONS: Bradykinin contributes to the systemic hemodynamic effects of long-term ACE inhibition in patients with heart failure. This mechanism may explain the apparent clinical differences between ACE inhibitors and angiotensin receptor blockers in the treatment of heart failure. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/15105283/Bradykinin_contributes_to_the_systemic_hemodynamic_effects_of_chronic_angiotensin_converting_enzyme_inhibition_in_patients_with_heart_failure_ L2 - https://www.ahajournals.org/doi/10.1161/01.ATV.0000129331.21092.1d?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -