ENHANCED VASOCONSTRICTOR RESPONSE OF THE ISOLATED PERFUSED CIRRHOTIC RAT-LIVER TO HUMORAL VASOCONSTRICTOR SUBSTANCES FOUND IN PORTAL VENOUS-BLOOD

Humoral vasoconstrictor factors in portal venous blood have an important influence on hepatic vascular tone. The aim of this study was to determine whether there is altered reactivity of the intrahepatic portal vascular bed of cirrhotic livers to such factors. Isolated perfused rat liver preparations (IPRLP) obtained from rats with carbon tetrachloride-induced cirrhosis and from normal controls were treated with small aliquots of fresh, heparinized venous blood (4% vol/vol) added to a synthetic perfusate composed of 2.5% bovine serum albumin in Krebs-Henseleit buffer. Compared with blood from the inferior vena cava, portal venous blood produced a greater increase in perfusion resistance of normal IPRLP (2.8 +/- 0.7 vs 15 +/- 3%, P < 0.05). There was no significant difference in the response of normal IPRLP to portal venous blood obtained from cirrhotic animals compared with portal blood from normal controls (10 +/- 4 vs 15 +/- 3%). However, cirrhotic IPRLP were significantly (P < 0.05) more responsive to portal venous blood than were control livers, regardless of whether the blood was obtained from control (28 +/- 6%) or cirrhotic (24 +/- 6%) rats. The response of both control and cirrhotic IPRLP to portal blood could be partially inhibited by the alpha-adrenoceptor antagonist phentolamine (5 x 10(-6)mol/L) and cirrhotic IPRLP were more responsive than controls to exogenous noradrenaline (518 +/- 27 vs 363 +/- 21%, P < 0.01). It is concluded that there is no significant difference in the intrahepatic vasoconstrictor activity of portal venous blood from normal or cirrhotic rats, and that the portal vascular bed of the cirrhotic rat liver shows enhanced vasoconstrictor responses not only to portal venous blood, obtained both from normal and cirrhotic rats, but also to exogenous noradrenaline.