Altered adrenergic responsiveness of endothelium-denuded hepatic arteries and portal veins in patients with cirrhosis

Gastroenterology. 1999 Feb;116(2):387-93. doi: 10.1016/s0016-5085(99)70136-8.

Abstract

Background & aims: Patients with cirrhosis are characterized by a reduced splanchnic vascular resistance and a hyporeactivity to adrenergic vasoconstrictors. So far, their adrenergic splanchnic vascular responsiveness has not been evaluated in vitro. We compared responses to alpha1- and beta2-adrenoceptor stimulation of hepatic arteries and portal veins of patients with cirrhosis undergoing transplantation with those of organ donors.

Methods: Isometric contractions of endothelium-denuded vessel rings were induced cumulatively by methoxamine and relaxations by isoproterenol. Results are expressed as percentage of the contraction obtained by 85 mmol/L KCl or of the relaxation obtained by 100 micromol/L papaverine, respectively.

Results: Maximal methoxamine-induced contractions were reduced in cirrhotic hepatic arteries (cirrhosis, 51.8% +/- 6.8%; donor, 89.9% +/- 6.6%; P < 0.01) and portal veins (cirrhosis, 49.2% +/- 6.4%; donor, 94.0% +/- 5.3%; P < 0.01). In cirrhosis, isoproterenol induced a less marked relaxation of hepatic arteries (cirrhosis, 46.6% +/- 3.2%; donor, 100.3% +/- 4.4%; P < 0. 01) but an increased relaxation of portal veins (cirrhosis, 41.9% +/- 6.2%; donor, 26.2% +/- 2.8%; P < 0.01).

Conclusions: In cirrhosis, endothelium-free hepatic arteries are hyporeactive to alpha1- and beta2-adrenoceptor agonists, and portal veins are hyporeactive to alpha1- but hyperreactive to beta2-adrenoceptor agonists. These findings support the in vivo findings of a hyporesponsiveness to adrenergic vasoconstrictors in patients with cirrhosis.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic Agonists / pharmacology*
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic beta-Agonists / pharmacology
  • Adult
  • Case-Control Studies
  • Endothelium, Vascular
  • Female
  • Hepatic Artery / drug effects*
  • Hepatic Artery / physiopathology*
  • Humans
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Liver Cirrhosis / physiopathology*
  • Liver Cirrhosis / surgery
  • Liver Transplantation
  • Male
  • Methoxamine / pharmacology
  • Middle Aged
  • Portal Vein / drug effects*
  • Portal Vein / physiopathology*
  • Receptors, Adrenergic / drug effects*
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / pharmacology

Substances

  • Adrenergic Agonists
  • Adrenergic alpha-Agonists
  • Adrenergic beta-Agonists
  • Receptors, Adrenergic
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Methoxamine
  • Isoproterenol