title: Flicker light-induced retinal vasodilation is unaffected by inhibition of epoxyeicosatrienoic acids and prostaglandins in humans.
abstract: OBJECTIVE
  To investigate the role of epoxyeicosatrienoic acids (EETs) and prostaglandins (PGs) in retinal blood vessel calibers and vasodilation during flicker light stimulation in humans.
  
  
  METHODS
  Twelve healthy nonsmokers participated in a balanced crossover study. Oral fluconazole 400 mg and dispersible aspirin 600 mg were used to inhibit production of EETs and PGs, respectively. Retinal imaging was performed 1 hour after drug ingestion with the Dynamic Vessel Analyzer. Resting calibers of selected vessel segments were recorded in measurement units (MU). Maximum percentage dilations during flicker stimulation were calculated from baseline calibers. We then studied six participants each after fluconazole and aspirin ingestions at 30-minute intervals for 2 hours. Within-subject differences were assessed by ANOVA and Dunnett-adjusted pairwise comparisons with significance taken at P < 0.05.
  
  
  RESULTS
  In crossover study participants, mean (SD) arteriole and venule dilations without drug administration were 4.4% (2.0%) and 4.6% (1.7%), respectively. Neither drug affected vasodilation during flicker stimulation. Mean (SD) resting arteriole and venule calibers on no-drug visits were 119.6 (10.6) MU and 145.7 (17.0) MU, respectively. Fluconazole reduced mean (±95% CI) resting venule calibers by 5.1 (4.3) MU. In repeated measures participants, neither drug affected vasodilations, but fluconazole reduced resting venule calibers over 2 hours (P < 0.001).
  
  
  CONCLUSIONS
  Epoxyeicosatrienoic acids and prostaglandins are unlikely to be primary mediators of flicker light-induced retinal vasodilation in humans. However, EETs may play a role in the regulation of retinal vascular tone and blood flow under resting physiological conditions.
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Noonan
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Thanh T
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Jenkins
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Ryan E K
authors.initials: RE
authors.lastname: Man
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: William J
authors.initials: WJ
authors.lastname: Best
authors.affiliation: Metabolomics Australia, School of Botany, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Dias
authors.affiliation: Metabolomics Australia, School of Botany, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Nirupama S
authors.initials: NS
authors.lastname: Jayasinghe
authors.affiliation: Metabolomics Australia, School of Botany, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ute
authors.initials: U
authors.lastname: Roessner
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia Singapore Eye Research Institute and Department of Ophthalmology, National University of Singapore, Singapore Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Ecosse L
authors.initials: EL
authors.lastname: Lamoureux
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000284:Administration, Oral; D018592:Cross-Over Studies; D065688:Cytochrome P-450 CYP2C9 Inhibitors / Q000008:administration & dosage; D015725:Fluconazole / Q000008:administration & dosage; D006801:Humans; D008027:Light; D010775:Photic Stimulation / Q000379:methods; D011453:Prostaglandins / Q000378:metabolism*; D012016:Reference Values; D012171:Retinal Vessels / Q000502:physiology*; D014664:Vasodilation / Q000528:radiation effects*
chemical_list: C515338:11,12-epoxyeicosatrienoic acid methyl ester; D065688:Cytochrome P-450 CYP2C9 Inhibitors; D011453:Prostaglandins; D015725:Fluconazole; D015126:8,11,14-Eicosatrienoic Acid
keywords: epoxyeicosatrienoic acids; functional imaging; neurovascular coupling; prostaglandins; retinal blood flow