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PURPOSE: To compare the vasoactive properties of the docosanoid unoprostone, its free acid, and different members of the prostanoid family on isolated perfused pig retinal arterioles in order to assess their potential to modulate retinal blood flow. METHODS: Segments of porcine retinal arterioles were dissected, cannulated, and perfused, and their diameter monitored during either intraluminal or extraluminal application of increasing doses (10-10 to 10-4 M) of either the docosanoid unoprostone isopropyl and its free acid or of selected prostanoids: prostaglandin (PG) F2α and thrombozane A2 analogue (U46619). Studies were performed on arterioles in their uncontracted state, and also during precontraction with endothelin-1 (10-9 M). The significance of any induced change in vessel diameter was assessed in relation to the initial vessel diameter or, in the case of endothelin-1 administration, to the contracted diameter with endothelin-1 alone. RESULTS: In normal-tone arterioles without endothelin-1 contraction, PGF2α and U46619 both produced a potent dose-dependent contraction, but neither unoprostone isopropyl nor unoprostone free acid had a significant vasoactive effect. In endothelin-1-contracted arterioles, U46619 produced further contraction, PGF2α produced a slight vasodilatation, and unoprostone isopropyl and its free acid produced a pronounced dilatation. CONCLUSIONS: Of the agents tested, unoprostone isopropyl and its free acid were the most potent vasodilators of endothelin-1-contracted pig retinal arteries. Members of the prostanoid family demonstrated a different effect on the diameter of isolated retinal arterioles compared with the docosanoids. Therefore, the potential exists for the docosanoid unoprostone to have a beneficial effect on retinal blood flow in addition to any reduction in intraocular pressure.
Dr Dao-Yi Yu, Lions Eye Institute, 2 Verdun Street, Nedlands, Perth, Western Australia 6009
11.4 Prostaglandins (Part of: 11 Medical treatment)