Systemic vascular endothelial cell dysfunction in normal pressure glaucoma

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; pD(2); 7.29 (SD 0.16) v 6.66 (0.19); p=0.03) and endothelin-1 (ET-1; pD(2), 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 (pD(2), 6,66 (0.19) v 7.66 (0.08); p=0.003) and ET-1 (pD(2), 8.72 (0.13) v9.66 (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.