Nitric oxide mediates the reduced vasoconstrictor response to angiotensin II in patients with preascitic cirrhosis

Ahmed Helmy, David Ernest Newby, Rajiv Jalan, Neil Russell Johnston, Peter Clive Hayes, David John Webb

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND/AIMS: Altered vascular responses to vasopressor agents contribute to the pathogenesis of the circulatory dysfunction in cirrhosis. This study aims to assess the role of endogenous nitric oxide (NO) in the reduced vascular responsiveness to angiotensin II (ANG-II) in eight patients with preascitic cirrhosis compared with eight age- and sex-matched healthy controls.

METHODS: Forearm blood flow (FBF) responses to sub-systemic, locally-active intra-brachial infusions of ANG-II were measured using venous occlusion plethysmography before and during the application of an 'NO-clamp', a balanced co-infusion of L-N(G)-monomethyl-arginine (a selective NO synthase inhibitor) and sodium nitroprusside (an exogenous NO donor) to block endogenous NO production and restore normal NO-mediated basal blood flow, respectively.

RESULTS: Before applying the 'NO-clamp', ANG-II caused dose-dependent reductions of FBF in both groups (P<0.001) that were significantly attenuated in the cirrhotic patients (P=0.012). In the presence of the 'NO-clamp', the ANG-II-mediated vasoconstriction was enhanced in cirrhotic patients (P<0.01), unchanged in controls, and now similar in both groups.

CONCLUSIONS: This study confirms that vasoconstriction to ANG-II is reduced in patients with preascitic cirrhosis, and suggests that this is principally due to enhanced NO generation mediated by ANG-II.

Original languageEnglish
Pages (from-to)44-50
Number of pages7
JournalJournal of Hepatology
Volume38
Issue number1
DOIs
Publication statusPublished - 1 Jan 2003

Keywords

  • Angiotensin II
  • Ascites
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors
  • Female
  • Forearm
  • Humans
  • Liver Cirrhosis
  • Male
  • Middle Aged
  • Nitric Oxide
  • Regional Blood Flow
  • Vasoconstriction
  • Vasoconstrictor Agents
  • omega-N-Methylarginine

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