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M. S. Torring, K. Holmgaard, A. Hessellund, C. Aalkjaer, T. Bek; The Vasorelaxing Effect of Carbonic Anhydrase Inhibitors on Porcine Retinal Arterioles in vitro Is Independent of Carbonic Anhydrase Inhibition. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2086. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Carbonic anhydrase inhibitors reduce the intraocular pressure leading to a better perfusion of the optic nerve and a protection of the optic nerve from ischemia. However, carbonic anhydrase inhibitors have also been shown to have a vasodilating effect on the blood vessels of the retina and the optic nerve head. The mechanisms underlying this effect are unknown, but evidence suggests that CO2, H+ and the perivascular retinal tissue may be involved. Therefore, the aim of the present study was to investigate whether the vasodilating effect of carbonic anhydrase inhibitors is due to carbonic anhydrase inhibition itself, and whether the effect depends on the perivascular retinal tissue.
Porcine retinal vessels were dissected with preserved perivascular retinal tissue, and were mounted in a myograph for isometric force measurements. After pre-contraction with the prostaglandin analogue U46619, concentration-response experiments were carried out with azetazolamide and dorzolamide before and after removal of the perivascular retina. The experiments were carried out in normal pH and acidosis (pH = 7.0) combined with respectively normocapnia and hypercapnia (pCO2=152 mmHg), as well as in buffer depleted from CO2 and HCO3-.
Carbonic anhydrase inhibitor induced vasodilation was inhibited in the presence of perivascular retinal tissue. The concentration-reponse curves were displaced to the left, representing higher sensitivity to the drug, by Dorzolamide as compared to Acetazolamide (p=0.15, n=5) and by acidosis compared to normal pH (p=0.03, n=6). However, neither hypercapnia (p=0.29, n=6) nor absence of CO2 and HCO3- in the buffer changed the sensitivity to the drugs (p=0.87, n=6).
The vasodilating effect of carbonic anhydrase inhibitors on porcine retinal vessels depends on the perivacular retinal tissue and the effect is not due to carbonic anhydrase inhibition.
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