Altered endothelin-1 vasoreactivity in patients with untreated normal-pressure glaucoma

Emer Henry, David E Newby, David J Webb, Patrick W F Hadoke, Colm J O'Brien

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Vasospasm, resulting from a generalized dysfunction in the vascular endothelium, is implicated in the development of normal-pressure glaucoma (NPG). Impaired endothelium-derived nitric oxide activity and abnormalities of the endothelin system suggest systemic endothelial cell dysfunction in patients with NPG. Endothelin (ET)-1 vasoreactivity was assessed in the peripheral circulation of patients with NPG.

METHODS: Forearm blood flow was measured using venous occlusion plethysmography in eight patients with untreated NPG and eight age- and sex-matched healthy volunteers during intra-arterial infusion of ET-1 (5 pmol/min) and, on a separate occasion, to BQ123, a selective endothelin-A receptor antagonist, (100 nmol/min). Blood pressure and heart rate were measured in the noninfused arm, and plasma ET-1 concentrations were measured using a radioimmunoassay.

RESULTS: Forearm blood flow fell during infusion of ET-1 (P<0.001 for both) to a similar extent in both groups (P=0.7; patients versus control subjects). In contrast, BQ123 increased forearm blood flow in both groups (P<0.001 for both), although the vasodilatation was lower in patients than in control subjects (P<0.001; patients versus control subjects). There was no difference in basal plasma ET-1 concentrations between the two groups (P=0.81; patients versus control subjects).

CONCLUSIONS: Despite normal responses to ET-1, patients with NPG have reduced vasodilatation in response to ETA-receptor antagonism. This could be due to attenuated ETA-receptor-mediated tone, increased ETB-receptor-mediated contraction or impaired ETB-receptor-mediated release of endothelial nitric oxide. These results are consistent with the authors' previous demonstration of systemic vascular dysfunction in patients with NPG.

Original languageEnglish
Pages (from-to)2528-32
Number of pages5
JournalInvestigative Ophthalmology & Visual Science
Volume47
Issue number6
DOIs
Publication statusPublished - Jun 2006

Keywords

  • Blood Flow Velocity
  • Blood Pressure
  • Endothelin A Receptor Antagonists
  • Endothelin-1
  • Endothelium, Vascular
  • Female
  • Forearm
  • Glaucoma, Open-Angle
  • Heart Rate
  • Humans
  • Intraocular Pressure
  • Male
  • Middle Aged
  • Peptides, Cyclic
  • Radioimmunoassay
  • Vasodilation

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