Portal hypertensive response to bradykinin in inflamed or cirrhotic rat livers is mediated by B-2-type receptors

Background: We have shown that the portal hypertensive response to bradykin in in normal rats is mediated by B-2 receptors. Methods: By using isolated and exsanguinated rat liver perfusion, we studie d the portal hypertensive response to bradykinin or des-Arg(9)-bradykinin ( B-1 agonist) in inflamed or cirrhotic rat livers. Livers were perfused with bovine serum albumin Krebs-Henseleit buffer (pH 7.4; 37 degreesC) at a con stant flow rate, in the absence or presence of des-Arg(9)[Leu(8)]-bradykini n or HOE 140 (B-1 and B-2 receptor antagonists, respectively). Bradykinin ( 140 nmol) or des-Arg(9)-bradykinin was injected as a bolus via the afferent route to the liver. Results: Basal perfusion pressure in liver-cirrhotic rats was higher than i n normal rats. In normal, inflamed, or liver-cirrhotic rats, the presence o f the B-1 antagonist did not change the portal hypertensive response to bra dykinin, while the B-2 antagonist abolished this response. A 140-nmol dose of des-Arg(9)-bradykinin did not change the perfusion pressure; 700 nmol of this B-1 agonist produced an insignificant perfusion pressure increase. Th e perfusion pressure increase induced by bradykinin in cirrhotic livers was lower than in normal livers. Conclusions: The portal hypertensive response to bradykinin in inflamed or cirrhotic rat livers is mediated by B-2 receptors, but not B-1 receptors, a nd there is a contracting hyporeactivity to bradykinin in cirrhotic rat liv ers. (C) 2001 Blackwell Science Asia Pty Ltd.