Portal vascular responsiveness to sympathetic stimulation and nitric oxide in cirrhotic rats.

AIMS/METHODS: The modulatory role of nitric oxide in portal vasoconstrictor responses was investigated in the isolated perfused liver of cirrhotic rats (induced by carbon tetrachloride/phenobarbitone; n = 6). Age-matched (n = 5) and phenobarbitone-treated rats (n = 5) served as controls.

RESULTS

At a constant flow rate of 5 ml/min there was no difference in basal perfusion pressure between the groups. Responses to electrical field stimulation of perivascular nerves caused frequency-dependent increases in perfusion pressure that were not significantly different between the groups. In contrast, dose-dependent vasoconstrictor responses to bolus injections of noradrenaline were up to two-fold greater than those observed in controls (p < 0.05). Vasoconstrictor responses to bolus injections of methoxamine (a selective alpha 1-adrenoceptor agonist) or adenosine 5'-triphosphate (ATP, a cotransmitter with noradrenaline in sympathetic nerves) were dose-dependent and similar between the groups. Infusion of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 30 microM) had no effect on basal tone or on responses to electrical field stimulation or injected agents. A step-wise increase in flow to 10, 15 and 20 ml/min produced a similar increase in perfusion pressure within each group. At increased flow, there was a decrease in responsiveness to noradrenaline (5 nmol) in preparations from all groups. In the presence of the K+ channel inhibitor glibenclamide (5 microM), the effect of noradrenaline in the cirrhotic group at flow rates of 5, 10 and 15 ml/min was maintained to a significantly greater extent than in either control group, suggesting that ATP-sensitive K+ channels in the portal venous bed may be activated in cirrhosis.

CONCLUSIONS

We conclude that portal vasoconstriction associated with noradrenaline, but not with sympathetic nerve stimulation, methoxamine or ATP, is enhanced in cirrhosis. Nitric oxide does not appear to play a modulatory role in these responses.