CLEAVAGE OF HIGH-MOLECULAR-WEIGHT KININOGEN IN ASCITES AND PLASMA OF PATIENTS WITH CIRRHOSIS

The vasoactive peptide bradykinin may be involved in the pathogenesis of vasodilation, which has been considered the initiating event of asc ites formation in cirrhotic patients. Since bradykinin is generated th rough the cleavage of high molecular weight kininogen (HK) by kallikre in, we looked for the cleavage of HK by an immunoblotting technique in plasma and ascitic fluid of 28 patients with cirrhosis of different e tiology. The majority of patients showed massive cleavage of HK in asc itic fluid (median 50% of total HK; range 23-100%). Patients with seve re ascites had more cleaved HK in plasma (29%; range 8-38%) than norma l subjects (22%; range 11-32) (P=0.02). Patients with high levels of p lasma renin activity (5-60 ng/ml/hour); which is considered a conseque nce of peripheral vasodilation, had more plasma cleaved HK (31%; range 18-38) (P=0.0097) than normals. Thus, our data support the view that cleavage of HK could play a role in the pathogenesis of vasodilation a nd ascites formation in patients with decompensated cirrhosis.