Bradykinin in the ascitic fluid of patients with liver cirrhosis.

Details

Serval ID
serval:BIB_0B8870AE1773
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Bradykinin in the ascitic fluid of patients with liver cirrhosis.
Journal
Clinical Science
Author(s)
Cugno M., Salerno F., Nussberger J., Bottasso B., Lorenzano E., Agostoni A.
ISSN
0143-5221
Publication state
Published
Issued date
12/2001
Peer-reviewed
Oui
Volume
101
Number
6
Pages
651-657
Language
english
Abstract
Bradykinin, a nonapeptide with vasodilatory and permeabilizing activity, is generated through the cleavage of high-M(r) ('high-molecular-weight') kininogen by kallikrein, and its generation is facilitated by plasmin. In the ascitic fluid of patients with cirrhosis, there is massive cleavage of high-M(r) kininogen and activation of fibrinolysis, but bradykinin has never been measured directly. In the ascitic fluid of 24 patients with cirrhosis, we measured bradykinin-(1-9)-nonapeptide levels by RIA after liquid-phase and subsequent HPLC extraction, and those of its catabolic product bradykininin-(1-5)-pentapeptide by ELISA after liquid-phase extraction. Cleaved high-M(r) kininogen, activated factor XII and plasmin-antiplasmin complexes were measured in ascitic fluid and plasma. Plasma renin activity (PRA) was also determined. As a control, we also analysed plasma from 24 healthy subjects matched for sex and age with the patients. In the ascitic fluid from patients with cirrhosis, the median bradykinin-(1-9) concentration was 3.3 fmol/ml (range 0.2-29.0 fmol/ml), and the median bradykinin-(1-5) concentration was 210 fmol/ml (range 58-7825 fmol/ml). The levels of bradykinin-(1-5) in ascitic fluid were higher in patients with refractory ascites [median 1091 fmol/ml (range 58-7825 fmol/ml)] than in patients with responsive ascites [134 fmol/ml (72-1084 fmol/ml)] (P=0.010). Ascitic fluid levels of bradykinin-(1-9) were not related to the severity of ascites. PRA was higher in patients with refractory ascites [23.0 ng x h(-1) x ml(-1) (7.9-80.0 ng.h(-1).ml(-1))] than in patients with responsive ascites [6.9 ng x h(-1) x ml(-1) (0.9-29.4 ng x h(-1) x ml(-1))] (P=0.002). In ascitic fluid, 48% (19-68%) of high-M(r) kininogen was cleaved, and plasmin-antiplasmin complexes were more concentrated than in plasma (P=0.0001). In conclusion, in the ascitic fluid of patients with cirrhosis, both bradykinin-(1-9) and bradykinin-(1-5) are present, with cleavage of high-M(r) kininogen and activation of fibrinolysis. The highest levels of the long-lived metabolite bradykinin-(1-5) were found in the ascitic fluid of patients with refractory ascites and high PRA. Activation of the kinin system may therefore be involved in decompensating cirrhosis, but a cause-effect relationship remains to be established.
Keywords
Adult, Aged, Antiplasmin/analysis, Ascitic Fluid/chemistry, Bradykinin/analysis, Electrophoresis, Polyacrylamide Gel, Factor XIIa/analysis, Female, Humans, Immunoblotting, Kininogens/analysis, Liver Cirrhosis/blood, Liver Cirrhosis/metabolism, Male, Middle Aged, Peptide Fragments/analysis, Plasmin/analysis, Renin/blood, Serum Albumin/analysis
Pubmed
Web of science
Create date
05/03/2008 17:41
Last modification date
20/08/2019 13:33
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