Jonathan E Noonan1, Gregory J Dusting1, Thanh T Nguyen1, Alicia J Jenkins2, Ryan E K Man1, William J Best1, Daniel A Dias3, Nirupama S Jayasinghe3, Ute Roessner3, Ecosse L Lamoureux4. 1. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia. 2. Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia. 3. Metabolomics Australia, School of Botany, University of Melbourne, Parkville, Victoria, Australia. 4. 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.
Abstract
PURPOSE: 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. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
RCT Entities:
PURPOSE: 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. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Authors: Alicia J Jenkins; Mugdha V Joglekar; Anandwardhan A Hardikar; Anthony C Keech; David N O'Neal; Andrzej S Januszewski Journal: Rev Diabet Stud Date: 2015-08-10
Authors: Aaron A Phillips; Franco Hn Chan; Mei Mu Zi Zheng; Andrei V Krassioukov; Philip N Ainslie Journal: J Cereb Blood Flow Metab Date: 2015-11-24 Impact factor: 6.200