Vasoconstrictor hyporeactivity can be reversed by antioxidants in patients with advanced alcoholic cirrhosis of the liver and ascites

Crit Care Med. 2005 Sep;33(9):2028-33. doi: 10.1097/01.ccm.0000178173.27923.eb.


Objective: Hyperdynamic circulation and systemic vasodilation complicate cirrhosis of the liver and are related to vasoconstrictor hyporeactivity. We investigated whether impaired vasoconstrictor responsiveness may be overcome by antioxidants in patients with decompensated alcoholic cirrhosis.

Design: Controlled clinical study.

Setting: University setting.

Patients: Nine patients with liver cirrhosis Child-Pugh grade C and nine healthy age-matched volunteers.

Interventions: Forearm blood flow responses to intra-arterial norepinephrine, angiotensin II, and the nitric oxide synthase inhibitor N-monomethyl-l-arginine were measured by strain-gauge plethysmography and compared between groups of patients. To assess the role of oxidative stress, the antioxidant vitamin C (24 mg/min) was administered locally into the brachial artery, and forearm blood flow responses were reassessed.

Measurements and main results: Plasma concentrations of vitamin C were lower in patients with cirrhosis (p < .05). In patients with cirrhosis, the reactivity to norepinephrine and angiotensin II was markedly reduced (p < .05 vs. controls). Coadministration of vitamin C completely restored the potency of vasoconstrictors to that in controls but had no effect in healthy subjects. No changes were observed in time-control experiments in cirrhosis patients (n = 3) employing vehicle coinfusion. The response to N-monomethyl-L-arginine was comparable between groups and not affected by vitamin C.

Conclusions: Oxidative stress with consumption of antioxidants seems to play an important role in the development of vasoconstrictor hyporeactivity in patients with cirrhosis. Antioxidant therapy may be a promising clinical approach to restore vasoconstrictor hyporeactivity in these patients.

MeSH terms

  • Angiotensin II / pharmacology
  • Antioxidants / therapeutic use*
  • Ascites / physiopathology*
  • Ascorbic Acid / therapeutic use
  • Female
  • Forearm / blood supply
  • Humans
  • Liver Cirrhosis, Alcoholic / physiopathology*
  • Male
  • Middle Aged
  • Norepinephrine / pharmacology
  • Oxidative Stress / drug effects
  • Vasoconstriction / drug effects*
  • Vasoconstrictor Agents / pharmacology
  • omega-N-Methylarginine / pharmacology


  • Antioxidants
  • Vasoconstrictor Agents
  • Angiotensin II
  • omega-N-Methylarginine
  • Ascorbic Acid
  • Norepinephrine