Altered endothelin-1 vasoreactivity in patients with untreated normal-pressure glaucoma.
OBJECTIVE
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.
Henry
Emer
E
Princess Alexandra Eye Pavilion, and The Clinical Pharmacology Unit, University of Edinburgh, Western General Hospital, United Kingdom. emerhenry1.@hotmail.com
Newby
David E
DE
Webb
David J
DJ
Hadoke
Patrick W F
PW
O'Brien
Colm J
CJ
D001783:Blood Flow Velocity; D001794:Blood Pressure; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D005902:Glaucoma, Open-Angle / Q000097:blood / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage; D011863:Radioimmunoassay; D014664:Vasodilation / Q000502:physiology*
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)