April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Dorzolamide-induced relaxation of porcine retinal arterioles in vitro depends on nitric oxide but not intracellular acidosis
Author Affiliations & Notes
  • Anders Raouf El-Galaly
    Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark
  • Sidse Kringelholt
    Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark
  • Mikkel Misfeldt
    Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark
  • Christian Aalkjaer
    Institute for Biomedicine (physiology), Aarhus University, Aarhus, Denmark
  • Toke Bek
    Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark
  • Footnotes
    Commercial Relationships Anders El-Galaly, None; Sidse Kringelholt, None; Mikkel Misfeldt, None; Christian Aalkjaer, None; Toke Bek, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4360. doi:
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      Anders Raouf El-Galaly, Sidse Kringelholt, Mikkel Misfeldt, Christian Aalkjaer, Toke Bek, ; Dorzolamide-induced relaxation of porcine retinal arterioles in vitro depends on nitric oxide but not intracellular acidosis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4360.

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

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Abstract

Purpose: The carbonic anhydrase inhibitor dorzolamide has been shown to induce relaxation of retinal arterioles and to increase blood flow and oxygenation in the retina. The relaxation effect has been shown to be independent of extracellular pH and CO2, whereas the role of intracellular pH and nitric oxide (NO) for the effect of dorzolamide is unknown.

Methods: Porcine retinal arterioles were mounted in a myograph and dorzolamide induced relaxation was studied after 1) the addition of the NO synthesis antagonists L-NAME (3x10-4 M) or ODQ (3x10-6 M), and 2) after loading of cells with the pH sensitive fluorophore SNARF-1-AM and studying changes in vascular tone and intracellular fluorescence after the induction of hypoxia, addition of lactate, and intracellular acidification with and without the presence of dorzolamide.

Results: Dorzolamide significantly reduced the tone of retinal arterioles in the presence of perivascular tissue (p<0.01) which could be significantly reduced by NO antagonists (p<0.05). Dorzolamide also increased intracellular acidification (p<0.03), but changes in vascular tone were not directly linked to intracellular acidosis.

Conclusions: Dorzolamide-induced vasorelaxation is independent of acidification in the extracellular and the intracellular space, but involves NO and other factors.

Keywords: 443 carbonic anhydrase • 688 retina • 436 blood supply  
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