Beraprost Sodium, a Stable Prostacyclin Analogue, Elicits Dilation of Isolated Porcine Retinal Arterioles: Roles of eNOS and Potassium Channels
Investigative Ophthalmology and Visual Science
Citation: Ono S, Nagaoka T, Omae T, et al. Beraprost sodium, a stable prostacyclin analogue, elicits dilation of isolated porcine retinal arterioles: roles of eNOS and potassium channels. Invest Ophthalmol Vis Sci. PURPOSE. Prostacyclin (PGI 2 ) is usually described as an endothelium-derived relaxing factor, but the vasoreactivity to PGI 2 in the retinal arterioles and the underlying mechanisms are not fully understood. We examined the effects of PGI 2 on the retinal microcirculation using
... culation using beraprost sodium (BPS), a stable PGI 2 analogue, and the signaling mechanisms involved in this vasomotor activity. METHODS. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded the diametric responses to BPS. RESULTS. Beraprost sodium elicited dose-dependent (0.1 pM-0.1 lM) vasodilation of the retinal arterioles that was abolished by the PGI 2 receptor (IP) antagonist CAY10441. Beraprost sodium-induced vasodilation decreased by 50% after the endothelium was removed and was inhibited by the nitric oxide (NO) synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) comparable with denudation. Inhibition of soluble guanylyl cyclase by 1H-1,2,4-oxadiazolo[4,3a]quinoxalin-1-one (ODQ) and blockage of protein kinase A (PKA) by Rp-8-Br-cAMPS were comparable to L-NAME. Beraprost sodium-induced vasodilation was also inhibited by the nonselective potassium channel inhibitor, tetraethylammonium, and the adenosine triphosphate-sensitive potassium (K ATP ) channel blocker, glibenclamide. Residual vasodilation in the presence of glibenclamide decreased further with subsequent application of ODQ. CONCLUSIONS. Beraprost sodium, a stable PGI 2 analogue, causes vasodilation of the retinal arterioles mediated via the IP receptor. The current findings suggest that BPS elicits endothelium-dependent and -independent dilation of the retinal arterioles mediated by NO induced by activation of PKA in the endothelium and the K ATP channel activation in the vascular smooth muscle, respectively.