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) 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.

No abstract

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.

Background/aims: Endothelial cell dysfunction in the ocular circulation may contribute to normal pressure glaucoma (NPG). This study aimed to investigate the contributions made by endothelium derived relaxing factors to relaxation of (1) subcutaneous resistance arteries from patients with NPG, and (2) porcine ciliary arteries. Methods: Human gluteal resistance arteries were isolated from seven patients with NPG and matched controls. Human and porcine arteries produced endothelium dependent relaxation when exposed to acetylcholine (ACh) (10 29 23610 25 M) or bradykinin (10 210 23610 26 M). Pharmacological agents were used to inhibit the nitric oxide pathway (L-arginine analogues, soluble guanylate cyclase inhibitor), endothelium derived hyperpolarising factor (EDHF) activity (potassium channel antagonists), and prostaglandin synthesis (cyclo-oxygenase inhibitors). Results: In all arteries, endothelium dependent relaxation was attenuated by nitric oxide (NO) inhibition or potassium channel blockade, but not by cyclo-oxygenase inhibition. Inhibition of ACh mediated relaxation by potassium channel antagonists was greater (p,0.05) in patients with NPG (Emax, 55.4% (SD 8.16%) relaxation, n = 4) than controls (Emax, 81.8% (6.0%), n = 5). In contrast, combined inhibition of NO synthase (NOS) and cyclo-oxygenase produced similar inhibition of ACh mediated relaxation in both groups. Conclusions: The enhanced contribution of EDHF to ACh mediated relaxation in systemic resistance arteries from NPG patients may contribute to the maintained endothelium mediated relaxation in these vessels. EDHF also contributes significantly to bradykinin mediated relaxation in porcine ocular ciliary arteries. Therefore, similar changes in the balance of relaxing factors in the ocular circulation could influence the response of the eye to vascular endothelial dysfunction in NPG.