May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Carbonic Anhydrase Inhibitors Elevate Optic Nerve Oxygen Tension in Pigs by Blocking Intracellular CA II
Author Affiliations & Notes
  • T. Eysteinsson
    Physiology, University of Iceland, Reykjavik, Iceland
  • D.B. Pedersen
    Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark
  • J.F. Kiilgaard
    Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark
  • M. la Cour
    Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark
  • E. Stefánsson
    Ophthalmology, University of Iceland, Reykjavik, Iceland
  • K. Bang
    Merck Sharp & Dohme Inc., Glostrup, Denmark
  • P.K. Jensen
    Merck Sharp & Dohme Inc., Glostrup, Denmark
  • Footnotes
    Commercial Relationships  T. Eysteinsson, MSD F; D.B. Pedersen, MSD F; J.F. Kiilgaard, MSD F; M. la Cour, MSD F; E. Stefánsson, MSD F; K. Bang, MSD E; P.K. Jensen, MSD F.
  • Footnotes
    Support  University of Copenhagen, Icelandic Research Council and Merck, Sharp & Dohme
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1302. doi:
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    • Get Citation

      T. Eysteinsson, D.B. Pedersen, J.F. Kiilgaard, M. la Cour, E. Stefánsson, K. Bang, P.K. Jensen; Carbonic Anhydrase Inhibitors Elevate Optic Nerve Oxygen Tension in Pigs by Blocking Intracellular CA II . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1302.

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

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Abstract

Abstract: : Purpose: To examine which isoenzymes of carbonic anhydrase (CA) mediate the effect of CA inhibition on the optic nerve oxygen tension in the pig. Methods: Optic nerve oxygen tension (ONPO2) was measured with a polarographic electrode placed in the vitreous, 0.5 mm over the optic disk in anaesthetized pigs. Carbonic anhydrase inhibitors acetazolamide, benzolamide, dorzolamide, 6-ethoxyzolamide and methazolamide were injected intravenously. Results: All CA inhibitors tested increased ONPO2, but to a different degree. Injection of 6-ethoxyzolamide (359 mg) increased the ONPO2 by a mean of 39%, dorzolamide (500 mg) by 43%, and methoxyzolamide (321 mg.) by 6.6%. Benzolamide (440 mg), which only blocks the membrane-bound CA IV, increased ONPO2 by 3%. The known ability of these CA inhibitors to block the intracellular CA II isoenzyme in vitro is a good predictor of their observed effect on ONPO2 (R2 = .97), while inhibition of the membrane-bound CA IV is not (R2 = .008). The CHCl3/buffer partition coefficients of these CA inhibitors, which are indicative of their lipophilicity, are also good predictors of their effect on ONPO2 (R2 = .50). Conclusions: CA inhibitors must be membrane permeable and have high affinity for CA II to elevate ONPO2 in pigs. Selective inhibition of CA IV with benzolamide has limited effect on ONPO2.

Keywords: pharmacology • optic disc • blood supply 
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