Systemic vascular endothelial cell dysfunction in normal pressure glaucoma.
OBJECTIVE
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.
Buckley
Christine
C
Department of Medicine, Royal Infirmary of Edinburgh, UK.
Hadoke
Patrick W F
PW
Henry
Emer
E
O'Brien
Colm
C
D000328:Adult; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005901:Glaucoma / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D012701:Serotonin