Effect of Rho Kinase Inhibitor Ripasudil (K-115) on Isolated Porcine Retinal Arterioles.

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  • Additional Information
    • Source:
      Publisher: Association For Ocular Pharmacology And Therapeutics Country of Publication: United States NLM ID: 9511091 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-7732 (Electronic) Linking ISSN: 10807683 NLM ISO Abbreviation: J Ocul Pharmacol Ther Subsets: MEDLINE
    • Publication Information:
      Publication: New York, NY : Association For Ocular Pharmacology And Therapeutics
      Original Publication: New York, NY : The Association, c1995-
    • Subject Terms:
      Arterioles/*drug effects ; Isoquinolines/*pharmacology ; Protein Kinase Inhibitors/*pharmacology ; Retinal Vessels/*drug effects ; Sulfonamides/*pharmacology ; rho-Associated Kinases/*antagonists & inhibitors; Animals ; Arterioles/metabolism ; Female ; Isoquinolines/chemistry ; Male ; Protein Kinase Inhibitors/chemistry ; Retinal Vessels/metabolism ; Sulfonamides/chemistry ; Swine ; rho-Associated Kinases/metabolism
    • Abstract:
      Purpose: To investigate the vasorelaxation effect of ripasudil (K-115), a novel Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, on isolated retinal arterioles. We determined whether the actions of ripasudil on the retinal microvascular diameter were dependent on the endothelium and/or potassium channels in the smooth muscle, with the goals of uncovering the signaling mechanisms required for this vasomotor activity and inhibiting the action of endothelin-1 (ET-1). Methods: In this in vitro study, we isolated porcine retinal arterioles, which were cannulated and pressurized without flow. We recorded diametric changes using videomicroscopic techniques. Results: In a dose-dependent (10 nM-30 μM) manner, retinal arterioles were relaxed in response to ripasudil [maximum % resting diameter, 160.3% ± 7.7% (mean ± standard error of the mean)]. The ripasudil-induced vasorelaxation was unaffected by endothelium removal, using nonselective potassium channel blocker tetraethylammonium, Ca 2+ -activated large-conductance potassium channel blocker iberiotoxin, voltage-gated potassium channel blocker 4-AP, ATP-sensitive potassium channel blocker glibenclamide, and inward rectifier potassium channel blocker BaCl 2 . Ripasudil prevented ET-1-caused vasoconstriction of the retinal arterioles regardless of the presence of endothelium to a similar extent. Conclusion: The ROCK inhibitor ripasudil elicits endothelium-independent relaxation and inhibits the action of ET-1 on the retinal arterioles. Determining the relaxation properties of ripasudil on the retinal microvasculature will likely support the development of potential therapies for glaucoma.
    • Contributed Indexing:
      Keywords: glaucoma; retinal arterioles; ripasudil; vasorelaxation
    • Accession Number:
      0 (Isoquinolines)
      0 (K-115)
      0 (Protein Kinase Inhibitors)
      0 (Sulfonamides)
      EC 2.7.11.1 (rho-Associated Kinases)
    • Publication Date:
      Date Created: 20201222 Date Completed: 20211129 Latest Revision: 20211129
    • Publication Date:
      20240829
    • Accession Number:
      10.1089/jop.2020.0082
    • Accession Number:
      33351704