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 N(G)-nitro-L-arginine methyl ester (L-NAME) inhibited UI-induced vasodilation. The large-conductance Ca(2+)-activated K channel (BK(Ca) 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 BK(Ca) channel activation.