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Systemic vascular endothelial cell dysfunction in normal pressure glaucoma

¹ Department of Medicine, Royal Infirmary of Edinburgh, UK
² Department of Medical Sciences, Western General Hospital, Edinburgh, UK
³ Department of Ophthalmology, Royal Infirmary of Edinburgh, UK
⁴ Institute of Ophthalmology, University College Dublin, Ireland

Correspondence to:
Correspondence to:
Dr C O'Brien, Mater Misericordiae Hospital, Eccles Street, Dublin 7, Ireland;
cobrien{at}mater.ie

Aim: Vascular risk factors, and particularly vasospasm, are thought to play a part in the pathogenesis of normal pressure glaucoma (NPG). This study aimed to determine whether the function of systemic resistance arteries was altered in patients with NPG.

Methods: Contractile and relaxant function was assessed in arteries dissected from gluteal fat biopsies (11 NPG, 12 control) using small vessel myography.

Results: Responses to K⁺ and noradrenaline were similar in patients and controls and were unaffected by endothelial removal. In contrast, responses to 5-hydroxytryptamine (5-HT; pD₂; 7.29 (SD 0.16) v 6.66 (0.19); p=0.03) and endothelin-1 (ET-1; pD₂, 9.12 (0.10) v 8.72 (0.13); p=0.03) were enhanced in arteries from patients with NPG. Removal of the endothelium enhanced responses to 5-HT (pD₂, 6.66 (0.19) v 7.66 (0.08); p=0.003) and ET-1 (pD₂, 8.72 (0.13) v 9.66 (0.39); p=0.02) in control arteries but not in those from patients. ET-1 mediated contraction in control and patient arteries was reduced in the presence of (10^-5 M) nifedipine. Endothelium dependent and independent relaxation was not impaired in arteries from patients.

Conclusions: This study has identified dysfunction of the systemic vascular endothelial cell in patients with normal pressure glaucoma. The vascular endothelium modulates contractile responses to 5-HT and ET-1 in human subcutaneous resistance arteries but this effect is lost in patients with NPG, indicating a selective defect in agonist mediated release of endothelium derived vasodilators. Selective antagonists of 5-HT and ET-1 may, therefore, help to prevent vasospasm in patients with NPG.

Keywords: vascular endothelium; human resistance arteries; normal pressure glaucoma

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