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Carbonic Anhydrase Inhibitors of Different Structures Dilate Pre-Contracted Porcine Retinal Arteries

Carbonic Anhydrase Inhibitors of Different Structures Dilate Pre-Contracted Porcine Retinal Arteries


Title: Carbonic Anhydrase Inhibitors of Different Structures Dilate Pre-Contracted Porcine Retinal Arteries
Author: Eysteinsson, Thor   orcid.org/0000-0002-9748-5854
Guðmundsdóttir, Hrönn
Harðarson, Arnar Össur
Berrino, Emanuela   orcid.org/0000-0002-4258-0678
Selleri, Silvia
Supuran, Claudiu   orcid.org/0000-0003-4262-0323
carta, fabrizio   orcid.org/0000-0002-1141-6146
Date: 2019-01-22
Language: English
Scope: 467
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Lífvísindasetur (HÍ)
Biomedical Center (UI)
Series: International Journal of Molecular Sciences;20(3)
ISSN: 1422-0067
DOI: 10.3390/ijms20030467
Subject: Carbonic anhydrase; Vascular tone; Vasodilation; Æðar; Ensím; Lífefnafræði
URI: https://hdl.handle.net/20.500.11815/1814

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Citation:

Eysteinsson, T.; Gudmundsdottir, H.; Hardarson, A.O.; Berrino, E.; Selleri, S.; Supuran, C.T.; Carta, F. Carbonic Anhydrase Inhibitors of Different Structures Dilate Pre-Contracted Porcine Retinal Arteries. International Journal of Molecular Sciences 2019, 20, 467.

Abstract:

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 EC 50 of each compound, ranging from 4.12 µM to 0.86 mM. All compounds had a lower mean EC 50 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 EC 50 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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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