September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Effects of intermittent hypoxia on rat ophthalmic artery reactivity: role of endothelin 1, oxidative stress and endothelium derived hyperpolarizing factors.
Author Affiliations & Notes
  • Marielle Mentek
    Fundamental research, INSERM U1042 - HP2 Laboratory, Grenoble, France
  • Diane Godin-Ribuot
    Fundamental research, INSERM U1042 - HP2 Laboratory, Grenoble, France
  • Marie Baldazza
    Fundamental research, INSERM U1042 - HP2 Laboratory, Grenoble, France
  • Jessica Morand
    Fundamental research, INSERM U1042 - HP2 Laboratory, Grenoble, France
  • Florent Aptel
    Ophthalmology, INSERM U1042 - HP2 Laboratory, Grenoble, France
  • Christophe Chiquet
    Ophthalmology, INSERM U1042 - HP2 Laboratory, Grenoble, France
  • Footnotes
    Commercial Relationships   Marielle Mentek, None; Diane Godin-Ribuot, None; Marie Baldazza, None; Jessica Morand, None; Florent Aptel, None; Christophe Chiquet, None
  • Footnotes
    Support  Fondation de France, Berthe Fouassier 2012-00029806,
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5023. doi:
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      Marielle Mentek, Diane Godin-Ribuot, Marie Baldazza, Jessica Morand, Florent Aptel, Christophe Chiquet; Effects of intermittent hypoxia on rat ophthalmic artery reactivity: role of endothelin 1, oxidative stress and endothelium derived hyperpolarizing factors.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5023.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Obstructive sleep apnea (OSA) is a common disease, characterized by recurrent desaturation-reoxygenation sequences. Intermittent hypoxia (IH) has been proposed as major component of OSA. OSA has been recently associated with a higher frequency of optic neuropathies. There are currently no pathophysiological data regarding the effect of HI or OSA on ocular vascular system. This study aims to characterize IH impact on rat ophthalmic artery (OA) reactivity. Particularly, the role of endothelin 1 (ET-1), oxidative stress and endothelium derived hyperpolarizing factors (EDHF) were studied.

Methods : Rats were exposed to 14 days IH (IH rats) or normoxia (NX rats). Using wire myography, OA reactivity was studied in response to ET-1, serotonin, phenylephrin . Vasorelaxation mediated by acetylcholine (Ach) was assessed in absence and presence of the Nitric Oxide Synthase (NOS) inhibitor L-NAME, the cyclooxygenase inhibitor indomethacin, the prostacyclin synthase inhibitor trans-2-phenylcyclopropylamine and the cytochrome P450 inhibitor fluconazole. Endothelin A receptor (ETRA) expression and superoxide anions production in OA were studied by immunohistolabelling and DHE labelling respectively.

Results : After 14 days IH, ETRA immunolabeling and superoxide anions expression in OA were increased by 22 % (p = 0.015) and 23 % (p = 0.04) respectively in IH rats. Ophthalmic artery contraction to 3.10-8 M ET-1 was increased by 16% (p<0.05) in IH rats. ETRA blockage (BQ-123) almost completely abolished contractile response to ET-1 in both groups. Endothelin B receptor (ETRB) blockage (BQ-788) increased response to ET-1 in NX rats but not in IH rats. Relaxation to acetylcholine (Ach) was significantly delayed in IH rats (p<0.0001). After NOS blockade with L-NAME, difference in Ach induced relaxation between groups was abolished. Cytochrome P450 inhibition by fluconazole had an opposite effect on response to Ach in NX and IH rats, increasing relaxation to Ach in IH rats and delaying it in NX rats.

Conclusions : Fourteen-day IH-exposure induces endothelial dysfunction in rat ophtalmic artery, associated with increase in oxidative stress and change in EDHF contribution to endothelial function. The increased contractile response to ET-1 in IH rats was due to an increase in ETRA -vasoconstriction and a decrease in ETRB vasorelaxation.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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