Key result
Carbonic anhydrase inhibitors caused vasodilation of pre-contracted porcine retinal arteries with varying efficacy, with mean EC50 values ranging from 4.12 µM to 0.86 mM.
Why the study?
Some carbonic anhydrase inhibitors act as vasodilators of retinal arteries, but the exact mechanism behind this vasodilatory effect is not yet clear.
Do carbonic anhydrase inhibitors of different structures dilate pre-contracted porcine retinal arteries?
Do carbonic anhydrase inhibitors of different structures dilate pre-contracted porcine retinal arteries?
Carbonic anhydrase inhibitors induce vasodilation in porcine retinal arteries, likely mediated by multiple CA isozymes including the membrane-bound isoform CA IV.
CAIs relax precontracted retinal arteries via multiple isozymes; leaves open in vivo relevance for retinal perfusion.
Carbonic anhydrase inhibitors (CAIs), such as dorzolamide (DZA), are used as anti-glaucoma drugs to lower intraocular pressure, but it has been found that some of these drugs act as vasodilators of retinal arteries. The exact mechanism behind the vasodilatory effect is not yet clear. Here we have addressed the issue by using small vessel myography to examine the effect of CAIs of the sulfonamide and coumarin type on the wall tension in isolated segments of porcine retinal arteries. Vessels were pre-contracted by the prostaglandin analog U-46619, and CAIs with varying affinity for five different carbonic anhydrase (CA) isoenzymes found in human tissue tested. We found that all compounds tested cause a vasodilation of pre-contracted retinal arteries, but with varying efficacy, as indicated by the calculated mean EC50 of each compound, ranging from 4.12 µM to 0.86 mM. All compounds had a lower mean EC50 compared to DZA. The dilation induced by benzolamide (BZA) and DZA was additive, suggesting that they may act on separate mechanisms. No clear pattern in efficacy and affinity for CA isoenzymes could be discerned from the results, although Compound 5, with a low affinity for all isoenzymes except the human (h) CA isoform IV, had the greatest potency, with the lowest EC50 and inducing the most rapid and profound dilation of the vessels. The results suggest that more than one isozyme of CA is involved in mediating its role in controlling vascular tone in retinal arteries, with a probable crucial role played by the membrane-bound isoform CA IV.
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Eysteinsson et al. (2019) studied Glaucoma / Retinal artery vasodilation. Carbonic anhydrase inhibitors vs. Dorzolamide was evaluated on Vasodilation (mean EC50). Carbonic anhydrase inhibitors caused vasodilation of pre-contracted porcine retinal arteries with varying efficacy, with mean EC50 values ranging from 4.12 µM to 0.86 mM.
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