June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
The Compensatory Role of Endothelium-Derived Hyperpolarizing Factor (EDHF) in Cholinergic Vasodilatation of the Mouse Ophthalmic Artery
Author Affiliations & Notes
  • Caroline Manicam
    Experimental Ophthalmology, University Medical Center Mainz, Mainz, Germany
  • Evgeny Goloborodko
    Experimental Ophthalmology, University Medical Center Mainz, Mainz, Germany
  • Norbert Pfeiffer
    Experimental Ophthalmology, University Medical Center Mainz, Mainz, Germany
  • Adrian Gericke
    Experimental Ophthalmology, University Medical Center Mainz, Mainz, Germany
  • Footnotes
    Commercial Relationships Caroline Manicam, None; Evgeny Goloborodko, None; Norbert Pfeiffer, None; Adrian Gericke, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4857. doi:
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      Caroline Manicam, Evgeny Goloborodko, Norbert Pfeiffer, Adrian Gericke; The Compensatory Role of Endothelium-Derived Hyperpolarizing Factor (EDHF) in Cholinergic Vasodilatation of the Mouse Ophthalmic Artery . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4857.

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

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Abstract

Purpose: The modulation of ocular blood flow is largely attributed to the vascular endothelium. In the mouse ophthalmic artery, endothelial nitric oxide synthase (eNOS) mediates only a part of the cholinergic dilatory response, while another yet unknown mechanism largely contributes towards acetylcholine-induced vasodilation. The aim of this study was to identify the compensatory mechanisms of endothelium-dependent vasodilation in mouse ophthalmic artery when eNOS is lacking.

Methods: Cholinergic vasodilatory responses of ophthalmic arteries from eNOS knockout mice (eNOS-/-) and respective wild type (WT) controls were studied in vitro using isolated vessels. Vascular preparations were incubated with various pharmacological inhibitors, and changes in luminal artery diameter in response to the endothelium-dependent vasodilator acetylcholine (ACh) were measured using video microscopy.

Results: The ACh-induced vasodilation was completely abolished in endothelium-denuded vessels whereas the nitric oxide donor, sodium nitroprusside, produced marked dilation in vessels with and without intact endothelium in WT and eNOS-/- mice. However, inhibition of NOS only caused a partial attenuation of the vasodilator responses in the WT mice but had no effect in the eNOS-/- mice. The involvement of EDHF was confirmed with 30 mM of potassium solution that completely abolished vasodilation in both mouse genotypes in the presence of NOS and cyclooxygenase (COX) inhibitors. Our data suggest that the arachidonic acid metabolites generated via the cytochrome P450 (CYP450) and lipoxygenase (LOX) pathways, the voltage-gated potassium channel Kv1.3 and gap junctions are the key players in modulating the ophthalmic artery diameter in the WT mice. In contrast, the lack of eNOS is compensated by the LOX pathway and voltage-gated potassium channels, but without CYP450 and gap junction involvement.

Conclusions: This study provides first evidence that the compensatory EDHF mechanisms differ between WT and eNOS-/- mice. While ACh-induced vasodilation in WT mouse ophthalmic arteries is mediated in part by NO and predominantly by EDHF, only EDHF mediates the response in eNOS-/- mice.

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