PURPOSE: Carbonic anhydrase inhibitors (CAIs) are used to reduce aqueous production in glaucoma, which includes a direct effect on the ciliary body. However, CAIs also affect ciliary blood flow, but the mechanisms of action of CAIs on the tone of intraocular ciliary arteries supplying the ciliary body have not been studied in detail. MATERIALS AND METHODS: The intraocular part of porcine ciliary arteries was isolated and mounted in a wire myograph system for isometric tension recordings. After contraction with the thromboxane analogue U46619, the vasorelaxing effect of the CAIs acetazolamide, brinzolamide and dorzolamide was studied. Subsequently, the involvement of the carbonic anhydrase reaction and nitric oxide (NO) in dorzolamide-induced vasorelaxation was characterized. RESULTS: All CAIs induced relaxation of contracted ciliary arteries, but the effect of dorzolamide was most pronounced. Dorzolamide-induced relaxation was unaffected by changes in pH and CO(2), and by removal of substrates to the carbonic anhydrase enzyme, but was abolished after inhibition of NO synthase and guanylyl cyclase and after removal of the vascular endothelium. CONCLUSIONS: Dorzolamide-induced vasorelaxation of ciliary arteries is independent of changes in the substances involved in the carbonic anhydrase reaction, but depends on NO and the vascular endothelium. The mechanism of action of dorzolamide in ocular disease may involve an effect on vascular tone mediated by NO.
PURPOSE: Carbonic anhydrase inhibitors (CAIs) are used to reduce aqueous production in glaucoma, which includes a direct effect on the ciliary body. However, CAIs also affect ciliary blood flow, but the mechanisms of action of CAIs on the tone of intraocular ciliary arteries supplying the ciliary body have not been studied in detail. MATERIALS AND METHODS: The intraocular part of porcine ciliary arteries was isolated and mounted in a wire myograph system for isometric tension recordings. After contraction with the thromboxane analogue U46619, the vasorelaxing effect of the CAIs acetazolamide, brinzolamide and dorzolamide was studied. Subsequently, the involvement of the carbonic anhydrase reaction and nitric oxide (NO) in dorzolamide-induced vasorelaxation was characterized. RESULTS: All CAIs induced relaxation of contracted ciliary arteries, but the effect of dorzolamide was most pronounced. Dorzolamide-induced relaxation was unaffected by changes in pH and CO(2), and by removal of substrates to the carbonic anhydrase enzyme, but was abolished after inhibition of NO synthase and guanylyl cyclase and after removal of the vascular endothelium. CONCLUSIONS:Dorzolamide-induced vasorelaxation of ciliary arteries is independent of changes in the substances involved in the carbonic anhydrase reaction, but depends on NO and the vascular endothelium. The mechanism of action of dorzolamide in ocular disease may involve an effect on vascular tone mediated by NO.
Authors: Anastasios G Konstas; Leopold Schmetterer; Andreas Katsanos; Cindy M L Hutnik; Gábor Holló; Luciano Quaranta; Miguel A Teus; Hannu Uusitalo; Norbert Pfeiffer; L Jay Katz Journal: Adv Ther Date: 2020-10-27 Impact factor: 3.845