This Article Full Text Full Text (PDF) All Versions of this Article: 24/6/1043    most recent 01.ATV.0000129331.21092.1dv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cruden, N. L.M. Articles by Newby, D. E. Search for Related Content PubMed PubMed Citation Articles by Cruden, N. L.M. Articles by Newby, D. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ENALAPRIL MALEATE LOSARTAN POTASSIUM Medline Plus Health Information Heart Failure Related Collections Congestive Cardiovascular Pharmacology

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1043.)
© 2004 American Heart Association, Inc.

Vascular Biology

Bradykinin Contributes to the Systemic Hemodynamic Effects of Chronic Angiotensin-Converting Enzyme Inhibition in Patients With Heart Failure

Nicholas L.M. Cruden; Fraser N. Witherow; David J. Webb; Keith A.A. Fox; David E. Newby

From the Centre for Cardiovascular Science, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.

Correspondence to Dr N.L.M. Cruden, Centre for Cardiovascular Science, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom EH16 4SB. E-mail nick.cruden{at}ed.ac.uk

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 µg/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·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 (P0.005 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.

In an invasive hemodynamic study of patients with heart failure, bradykinin antagonism caused changes in systemic hemodynamic variables when treated with enalapril. These findings suggest that bradykinin contributes to the systemic hemodynamic effects of ACE inhibition and may explain the apparent clinical differences between ACE inhibitors and angiotensin receptor blockers.

Key Words: ACE inhibitors • bradykinin • heart failure • hemodynamics • pharmacology

This article has been cited by other articles:

				B. Pitt RAAS inhibition/blockade in patients with cardiovascular disease: implications of recent large-scale randomised trials for clinical practice Heart, August 1, 2009; 95(15): 1205 - 1208. [Full Text] [PDF]

				J. P. Langrish, N. L. Mills, L. E. Bath, P. Warner, D. J. Webb, C. J. Kelnar, H. O.D. Critchley, D. E. Newby, and W. H. B. Wallace Cardiovascular Effects of Physiological and Standard Sex Steroid Replacement Regimens in Premature Ovarian Failure Hypertension, May 1, 2009; 53(5): 805 - 811. [Abstract] [Full Text] [PDF]

				J. LeFebvre, A. Shintani, T. Gebretsadik, J. R. Petro, L. J. Murphey, and N. J. Brown Bradykinin B2 Receptor Does Not Contribute to Blood Pressure Lowering during AT1 Receptor Blockade J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1261 - 1267. [Abstract] [Full Text] [PDF]

				Z. Chen, P. A. Deddish, R. D. Minshall, R. P. Becker, E. G. Erdos, and F. Tan Human ACE and bradykinin B2 receptors form a complex at the plasma membrane FASEB J, November 1, 2006; 20(13): 2261 - 2270. [Abstract] [Full Text] [PDF]

				J. McMurray, S. Solomon, K. Pieper, S. Reed, J. Rouleau, E. Velazquez, H. White, J. Howlett, K. Swedberg, A. Maggioni, et al. The Effect of Valsartan, Captopril, or Both on Atherosclerotic Events After Acute Myocardial Infarction: An Analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT) J. Am. Coll. Cardiol., February 21, 2006; 47(4): 726 - 733. [Abstract] [Full Text] [PDF]

				N. L.M. Cruden, G. H. Tse, K. A.A. Fox, C. A. Ludlam, I. Megson, and D. E. Newby B1 Kinin Receptor Does Not Contribute to Vascular Tone or Tissue Plasminogen Activator Release in the Peripheral Circulation of Patients With Heart Failure Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 772 - 777. [Abstract] [Full Text] [PDF]

				D. J. Campbell, H. Krum, and M. D. Esler Losartan Increases Bradykinin Levels in Hypertensive Humans Circulation, January 25, 2005; 111(3): 315 - 320. [Abstract] [Full Text] [PDF]