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

J Hepatol. 1996 Jul;25(1):90-7. doi: 10.1016/s0168-8278(96)80333-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Electric Stimulation
  • Liver Cirrhosis, Experimental / physiopathology*
  • Male
  • Methoxamine / pharmacology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / physiology*
  • Norepinephrine / pharmacology
  • Portal Pressure / drug effects
  • Portal System / physiopathology*
  • Rats
  • Rats, Wistar
  • Sympathetic Nervous System / physiology*
  • Vasoconstriction / drug effects


  • Nitric Oxide
  • Adenosine Triphosphate
  • Methoxamine
  • NG-Nitroarginine Methyl Ester
  • Norepinephrine