Altered peripheral vascular responses to exogenous and endogenous endothelin-1 in patients with well-compensated cirrhosis

A Helmy, R Jalan, D E Newby, N R Johnston, P C Hayes, D J Webb

Research output: Contribution to journalArticlepeer-review

Abstract

Plasma endothelin concentrations are elevated in cirrhosis and correlate with disease severity. This study assessed forearm vascular responses to exogenous endothelin-1 (ET-1), and evaluated the contribution of endogenous ET-1 to the maintenance of basal peripheral vascular tone in patients with well-compensated cirrhosis (n = 11) and matched healthy controls (n = 8). Bilateral forearm blood flow (FBF) was measured at baseline and following unilateral, subsystemic, intrabrachial artery infusions of ET-1 (2 and 6 pmol/min); BQ-123, a selective ET(A) receptor antagonist (3 and 10 nmol/min); and BQ-788, a selective ET(B) receptor antagonist (0.3 and 1 nmol/min) using venous occlusion plethysmography. Baseline systemic hemodynamics and plasma ET-1 and big ET-1 concentrations were measured using electrical bioimpedance and radioimmunoassay, respectively. Patients and controls had similar baseline FBF, systemic hemodynamics, and plasma ET-1 and big ET-1 concentrations. In both groups, ET-1 and BQ-788 caused significant vasoconstriction (P < .001) and BQ-123 caused significant vasodilatation (P < .001). Compared with controls, cirrhotic patients had attenuated ET-1 responses (P < .001), augmented BQ-123 responses (P < .001), and similar BQ-788 responses (P = .62). Despite normal systemic hemodynamics and plasma ET-1 concentrations, forearm vascular responses to exogenous ET-1 are reduced in cirrhotic patients. The augmented vasodilatation to BQ-123 in cirrhotic patients is consistent with a compensated vasodilated state, and a greater contribution of ET-1 to the maintenance of basal vascular tone acting through the ET(A) receptor.

Original languageEnglish
Pages (from-to)826-31
Number of pages6
JournalHepatology
Volume33
Issue number4
DOIs
Publication statusPublished - 1 Apr 2001

Keywords

  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Endothelins
  • Female
  • Forearm
  • Hemodynamics
  • Humans
  • Liver Cirrhosis
  • Male
  • Middle Aged
  • Oligopeptides
  • Peptides, Cyclic
  • Piperidines
  • Protein Precursors
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Reference Values
  • Vascular Resistance

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