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Bradykinin Does Not Contribute to Peripheral Vascular Tone in Patients With Cirrhosis and Ascites

Helmy, Ahmed MB, ChB(Hons), PhD*; Ferguson, James W. MB, ChB, MRCP*; Hayes, Peter C. MD, PhD, FRCP*; Newby, David E. PhD, DM, FRCP; Webb, David J. MD, DSc, FRCP, FRSE

Journal of Cardiovascular Pharmacology:
doi: 10.1097/01.fjc.0000211727.23304.49
Original Articles
Abstract

Bradykinin is an endothelium-dependent vasodilator and inflammatory mediator. The aim of the present study was to examine the effects of bradykinin on peripheral vascular tone in patients with cirrhosis and ascites. Forearm blood flow was measured using venous occlusion plethysmography in 8 patients with biopsy-proven alcohol-induced cirrhosis, ascites, and portal hypertension, and 8 age- and sex-matched healthy controls. On 1 occasion, subjects received an intrabrachial infusion of the selective bradykinin antagonist B9340 (1.5–13.5 nmol/min) followed by a control vasoconstrictor norepinephrine (60–540 pmol/min), and on another occasion bradykinin (100–900 pmol/min) followed by the endothelium-independent vasodilator, sodium nitroprusside (SNP, 2–8 μg/min). Bradykinin and SNP caused a dose-dependent vasodilatation (P<0.001 for both) that did not differ between the 2 groups. Although norepinephrine caused a similar dose-dependent vasoconstriction in both groups (P<0.001), B9340 had no effect on forearm blood flow in either group (at 13.5 nmol/min in patients; −5%, 95% CI −13−3). Bradykinin does not provide a major contribution to the maintenance of peripheral vascular tone in patients with cirrhosis and ascites. Our findings also suggest that, in contrast to cardiovascular disease, patients with liver cirrhosis do not have marked endothelial dysfunction.

Author Information

Departments of *Hepatology

Cardiology, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK

Clinical Pharmacology Unit and Research Centre, Department of Medical Sciences, University of Edinburgh, Western General Hospital, Edinburgh

Reprints: James Ferguson, Liver Unit, Royal Infirmary, 51 Little France Crescent, Edinburgh, EH16 4SU, UK (e-mail: j.w.ferguson@ed.ac.uk).

Received for publication September 15, 2005; accepted November 18, 2005

© 2006 Lippincott Williams & Wilkins, Inc.