Membrane Permeability Is Required for the Vasodilatory Effect of Carbonic Anhydrase Inhibitors in Porcine Retinal Arteries

• Published in: International Journal of Molecular Sciences
• Main Authors: Eysteinsson, Thor, García-Llorca, Andrea, Hardarson, Arnar Oessur, Vullo, Daniela, Carta, Fabrizio, Supuran, Claudiu T.
• Other Authors: Faculty of Medicine, Surgical Services, Faculty of Nursing and Midwifery
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2023
• Subjects: arterial wall tension; carbonic anhydrase; membrane impermeable; myography; porcine; Carbonic Anhydrase Inhibitors/pharmacology; Animals; Swine; Benzolamide/pharmacology; Retinal Artery; Permeability; Vasodilation; Molecular Biology; Spectroscopy; Catalysis; Inorganic Chemistry; Computer Science Applications; Physical and Theoretical Chemistry; Organic Chemistry; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/4829; https://doi.org/10.3390/ijms24098140

Funding Information: This research was funded in part by the Helga Jónsdóttir and Sigurlidi Kristjánsson Memorial Fund, and the University of Iceland Research Fund. Publisher Copyright: © 2023 by the authors. It has been demonstrated previously that a variety of carbonic anhydrase inhibitors (CAIs) can induce vasodilation in pre-contracted retinal arteriolar segments although with different efficacy and potency. Since the CAIs tested so far are able to permeate cell membranes and inhibit both intracellular and extracellular isoforms of the enzyme, it is not clear whether extra- or intracellular isoforms or mechanisms are mediating their vasodilatory effects. By means of small wire myography, we have tested the effects of four new CAIs on wall tension in pre-contracted retinal arteriolar segments that demonstrably do not enter cell membranes but have high affinity to both cytosolic and membrane-bound isoforms of CA. At concentrations between 10−6 M to 10−3 M, none of the four membrane impermeant CAIs had any significant effect on arteriolar wall tension, while the membrane permeant CAI benzolamide (10−3 M) fully dilated all arteriolar segments tested. This suggests that CAI act as vasodilators through cellular mechanisms located in the cytoplasm of vascular cells. Peer reviewed