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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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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.
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