Purchase this article with an account.
Ichiro Tanano, Taiji Nagaoka, Tsuneaki Omae, Takayuki Kamiya, Shinji Ono, Akitoshi Yoshida; Dilation of Porcine Retinal Arterioles via a cAMP/Protein Kinase A and AMP-Activated Protein Kinase-Dependent Mechanism with Cilostazol. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6854.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Cilostazol, a selective inhibitor of phosphodiesterase 3, has antiplatelet aggregation and peripheral vasodilation effects. We examined the effects of cilostazol on the retinal microvascular diameter to determine if they depend on the endothelium and/or potassium (K) channels in smooth muscle to reveal the signaling mechanisms involved in this vasomotor activity.
Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded diametric responses to cilostazol.
The retinal arterioles dilated in a cilostazol concentration-dependent (0.1 nM-10 µM) manner and decreased by 60% after endothelial removal. The nitric oxide (NO) synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), inhibited cilostazol-induced vasodilation comparable to denudation. Inhibition of soluble guanylyl cyclase and blockade of protein kinase A (PKA) were comparable to L-NAME. Compound C, an AMP-activated protein kinase (AMPK) inhibitor, partially inhibited cilostazol-induced vasodilation, which exhibited a weaker inhibitory effect on cilostazol-induced vasodilation than blockade of PKA. The large-conductance Ca2+-activated K channel (BK channel) blocker, iberiotoxin, also inhibited cilostazol-induced vasodilation.
Cilostazol elicits endothelium-dependent and -independent dilation of retinal arterioles mediated by NO release and BK channel activation, respectively.
This PDF is available to Subscribers Only