Vasodilatory mechanisms of unoprostone isopropyl in isolated porcine retinal arterioles

PURPOSE To clarify the vasodilatory mechanism of unoprostone isopropyl (UI), we examined its effects on the retinal microvascular diameter to determine the dependence on the endothelium and/or smooth muscle to reveal 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 UI. RESULTS The retinal arterioles dilated in response to UI in a dose-dependent (100 pM-10 µM) manner. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) inhibited UI-induced vasodilation. The large-conductance Ca2+-activated K channel (BKCa channel) blocker iberiotoxin also inhibited UI-induced vasodilation. The residual vasodilation after L-NAME was eliminated with co-administration of iberiotoxin. CONCLUSIONS UI elicits dilation of the retinal arterioles mediated by NO release and BKCa channel activation.