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Abstract #91775 Published in IGR 21-4
Effect of Rho Kinase Inhibitor Ripasudil (K-115) on Isolated Porcine Retinal Arterioles
Kamiya T; Omae T; Nakabayashi S; Takahashi K; Tanner A; Yoshida AJournal of Ocular Pharmacology and Therapeutics 2021; 37: 104-111
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). In this study, we isolated porcine retinal arterioles, which were cannulated and pressurized without flow. We recorded diametric changes using videomicroscopic techniques. 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-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. Ripasudil prevented ET-1-caused vasoconstriction of the retinal arterioles regardless of the presence of endothelium to a similar extent. 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.
Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
Full articleClassification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
6.11 Bloodflow measurements (Part of: 6 Clinical examination methods)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)
