Abstract
Purpose
Retinal hypoxia with consequent changes in blood flow play a role in a number of vision-threatening diseases, such as diabetic retinopathy. Previous studies have shown that the inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) products are involved in the diameter regulation of the retinal vessels during hypoxia. Therefore, the aim of the present study was to examine the effects of an NO donor combined with COX inhibition on the diameter regulation of retinal vessels during hypoxia in normal persons.
Methods
Twenty normal persons aged 21–47 years were examined. The Dynamic Vessel Analyzer (DVA) was used to measure retinal vessel diameters at rest, during isometric exercise, and during flicker stimulation. The measurements were performed during normoxia and hypoxia before and after sublingual administration of the NO donor nitroglycerin, and were repeated on a second study day after topical administration of the COX-inhibitor diclofenac.
Results
The resting diameter of arterioles and venules increased significantly during hypoxia (p < 0.0001). Hypoxia also significantly reduced the arteriolar constriction during isometric exercise, and the dilatation of the arterioles and venules during flicker stimulation (p < 0.0001). Diclofenac further reduced the arteriolar constriction induced by isometric exercise during hypoxia (p = 0.005). However, the NO-donor nitroglycerin had no effect on vascular diameters.
Conclusion
Diameter regulation of retinal vessels during hypoxia in normal persons can be influenced by the inhibition of COX products, but not by increasing the NO concentration. The findings suggest that the vasoactive effects of NO on retinal arterioles during hypoxia are saturated in normal persons.
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The study was supported by Jochum and Marie Jensen’s Foundation, Synoptikfonden and the VELUX Foundation
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All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.
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The study was supported by Jochum and Marie Jensen’s Foundation, Synoptikfonden and the VELUX Foundation. The sponsors had no role in the design or conduct of this research.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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ClinicalTrials registration number: NCT02059018
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Kaya, M.Y., Petersen, L. & Bek, T. Lack of effect of nitroglycerin on the diameter response of larger retinal arterioles in normal persons during hypoxia. Graefes Arch Clin Exp Ophthalmol 254, 277–283 (2016). https://doi.org/10.1007/s00417-015-3227-4
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DOI: https://doi.org/10.1007/s00417-015-3227-4