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

International Journal of Molecular Sciences

Hrönn Gudmundsdottir¹  Arnar Oessur Hardarson¹  Thor Eysteinsson¹  Fabrizio Carta²  Silvia Selleri²  Claudiu T. Supuran²  Emanuela Berrino² 

[1] Department of Physiology, BioMedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland;NEUROFARBA Department, University of Florence, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy;

关键词: carbonic anhydrase;    vasodilation;    vascular tone;   

DOI  :  10.3390/ijms20030467

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown