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Thor Eysteinsson, Arnar Ossur Hardarson, Fabrizio Carta, Claudiu T. Supuran; Membrane permeable but not impermeable carbonic anhydrase inhibitors dilate precontracted porcine retinal arteries. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4606.
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© ARVO (1962-2015); The Authors (2016-present)
Carbonic anhydrase inhibitors (CAI's) that are used for glaucoma treatment have also been found to cause vasodilation of retinal arteries, and to elevate retinal and optic nerve PO2. However, the mechanism for this effect is not fully understood. The purpose of this study is to identify which carbonic anhydrase isoenzymes produce vasodilation when inhibited, and whether the isoenzymes involved are located intracellularly or on the surface of cell membranes, through the use of selective membrane permeable and impermeable CAI's.
Dissected segments of porcine retinal arteries were mounted in a wire myograph for measurement of contractile activity and precontracted with 10-6M U-46619, a prostaglandin analog, added to the organ bath. When the vascular tone had stabilized the CAI's tested, which have distinct affinity for different carbonic anhydrase isoenzymes, and vary in membrane permeability, were applied separately to the bath, and the effects of each on the tone recorded. Results are presented as mean ± SEM percentage of the maximum vasodilation, as compared to the prior vasoconstriction per mm, induced by 10-6M U-46619. Two-tailed Student’s t-test was used for statistical analysis of the results.
The membrane permeable CAI dorzolamide (10-3M ) induced a mean relaxation of porcine retinal arteries by 76 ± 8% (P< 0.02) when precontracted with U-46619. Benzolamide, claimed to be a relatively membrane impermeable CAI, induced a significant mean relaxation of 85 ± 8% (P< 0.01) at 10-3M after U-46629 induced vasoconstriction. The pyridinium derivative FC5-207A (10-3M ), a membrane impermeable CAI, however had no effects on the vascular tone of retinal arteries precontracted by U-45519.
Known membrane permeable carbonic anhydrase inhibitors induce vasodilation in precontracted porcine retinal arteries, while membrane impermeable inhibitors do not, suggesting that cytosolic isoenzymes of carbonic anhydrase are involved in mediating the vasodilation. The results further suggest that benzolamide is likely a membrane permeable CAI.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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