Article Text

Download PDFPDF
Haeme oxygenase mediates hyporeactivity to phenylephrine in the mesenteric vessels of cirrhotic rats with ascites
  1. M Bolognesi,
  2. D Sacerdoti,
  3. M Di Pascoli,
  4. P Angeli,
  5. S Quarta,
  6. A Sticca,
  7. P Pontisso,
  8. C Merkel,
  9. A Gatta
  1. Department of Clinical and Experimental Medicine, University of Padova, Italy
  1. Correspondence to:
    Dr M Bolognesi
    Clinica Medica 5, Dipartimento di Medicina Clinica e Sperimentale, Policlinico Universitario, Via Giustiniani 2, 35128 Padova, Italy;


Background and aims: Haeme oxygenase could play a role in the pathogenesis of arterial vasodilation in cirrhosis. The aim of this study was to verify the role of haeme oxygenase in the hyporesponsiveness to phenylephrine of small mesenteric arteries in rats with CCl4 induced cirrhosis, with and without ascites.

Methods: Pressurised small resistance mesenteric arteries were challenged with increasing doses of phenylephrine. Dose-response curves were evaluated under basal conditions, after inhibition of haeme oxygenase with chromium-mesoporphyrin, after inhibition of nitric oxide synthase (NOS) with NG-nitro-L-arginine-methyl-ester (L-NAME), and then after inhibition of both NOS and haeme oxygenase. Haeme oxygenase protein expression was also analysed.

Results: Twenty six control rats and 35 rats with cirrhosis (17 with and 18 without ascites) were studied. Response to phenylephrine was lower in non-ascitic and ascitic cirrhosis than in controls. Chromium-mesoporphyrin increased the response to phenylephrine only in ascitic cirrhosis (p<0.001). L-NAME increased the response to phenylephrine in controls (p<0.001) and in ascitic and non-ascitic cirrhosis (p = 0.002, p<0.001, respectively) but the final response in non-ascitic cirrhosis was similar to that of control rats while it remained impaired in ascitic cirrhosis. Addition of chromium-mesoporphyrin to L-NAME improved the response to phenylephrine in ascitic cirrhosis (p<0.01), with final values not different from those of the other two groups. Protein expression of the inducible isoform of haeme oxygenase was increased in the mesenteric vessels of cirrhotic rats.

Conclusion: Haeme oxygenase mediates hyporeactivity to phenylephrine in the mesenteric vessels of experimental cirrhosis with ascites. NOS plays a major role only in the first stage of the disease.

  • CO, carbon monoxide
  • CrMP, chromium mesoporphyrin
  • EC(50), molar concentration of phenylephrine causing 50% contraction
  • eNOS, endothelial nitric oxide synthase
  • HO, haeme oxygenase
  • HO-1, inducible haeme oxygenase
  • HO-2, constitutive haeme oxygenase
  • iNOS, inducible nitric oxide synthase
  • L-NAME, NG-nitro-L-arginine methyl ester
  • NO, nitric oxide
  • NOS, nitric oxide synthase
  • PE, phenylephrine
  • PSS, polysalin solution
  • portal hypertension
  • experimental liver cirrhosis
  • mesenteric resistance arteries
  • chromium mesoporphyrin
  • nitric oxide

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published online first 10 June 2005

  • Conflict of interest: None declared.