Portal hypertensive response to bradykinin in inflamed or cirrhotic rat livers is mediated by B2-type receptors.
BACKGROUND
We have shown that the portal hypertensive response to bradykinin in normal rats is mediated by B2 receptors.


METHODS
By using isolated and exsanguinated rat liver perfusion, we studied the portal hypertensive response to bradykinin or des-Arg9-bradykinin (B1 agonist) in inflamed or cirrhotic rat livers. Livers were perfused with bovine serum albumin Krebs-Henseleit buffer (pH 7.4; 37 degrees C) at a constant flow rate, in the absence or presence of des-Arg9[Leu8]-bradykinin or HOE 140 (B1 and B2 receptor antagonists, respectively). Bradykinin (140 nmol) or des-Arg9-bradykinin was injected as a bolus via the afferent route to the liver.


RESULTS
Basal perfusion pressure in liver-cirrhotic rats was higher than in normal rats. In normal, inflamed, or liver-cirrhotic rats, the presence of the B1 antagonist did not change the portal hypertensive response to bradykinin, while the B2 antagonist abolished this response. A 140-nmol dose of des-Arg9-bradykinin did not change the perfusion pressure; 700 nmol of this B1 agonist produced an insignificant perfusion pressure increase. The 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 B2 receptors, but not B1 receptors, and there is a contracting hyporeactivity to bradykinin in cirrhotic rat livers.
Loureiro-Silva
M R
MR
Laboratory of Experimental Hepatology (Núcleo de Metabolismo Hepático), Universidade Federal de São Paulo, Brazil.
Molina
H M
HM
Borges
D R
DR
D000704:Analysis of Variance; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002251:Carbon Tetrachloride; D006975:Hypertension, Portal / Q000188:drug therapy*; D007249:Inflammation; D007609:Kallidin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000378:metabolism*; D014425:Turpentine
D018002:Receptors, Bradykinin; D007609:Kallidin; C052787:kallidin, des-Arg(10)-; D002251:Carbon Tetrachloride; D001920:Bradykinin; D014425:Turpentine