Diameter Changes of Retinal Arterioles During Acute Hypoxia In Vivo are Modified by the Inhibition of Nitric Oxide and Prostaglandin Synthesis

Abstract

ABSTRACTPurpose: Inhibition of cyclooxygenase (COX) and nitric oxide synthesis (NOS) has previously been shown to modify hypoxia-induced relaxation of retinal arterioles in vitro. The purpose of the present study was to investigate whether these findings can be reproduced in vivo.Methods: Twenty healthy persons aged 20–55 years were examined. Using the dynamic vessels analyzer (DVA), the resting diameter and diameter changes during isometric exercise and flicker stimulation were studied before and during breathing of a hypoxic gas mixture. The examinations were carried out before and during intravenous infusion of the NOS-inhibitor l-NMMA, and were repeated on a second study day after topical administration of the COX-inhibitor diclofenac.Results: The resting diameter of retinal arterioles increased significantly during hypoxia and decreased significantly during l-NMMA infusion (p < 0.0001) which compensated for changes in the blood pressure. During hypoxia and l-NMMA infusion together contraction of retinal arterioles could not compensate for the increased blood pressure as assessed by a gain factor significantly lower than one (p = 0.002).The arteriolar contraction induced by isometric exercise was significantly reduced by diclofenac and flicker-induced dilatation of retinal arterioles was increased during l-NMMA infusion (p < 0.0001).Conclusion: Diameter changes of retinal vessels during acute hypoxia in vivo are modified by inhibiting NO and prostaglandin synthesis. The evidence points to possible new targets of intervention on the diameter regulation of retinal arterioles in diseases where retinal hypoxia is part of the disease pathogenesis.