Effect Of Rho Kinase Inhibitor Ripasudil (K-115) On Isolated Porcine Retinal Arterioles

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 mu M) 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, Ca2+-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 BaCl2. 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.