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1 From the Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth; 2 Lions Eye Institute, Nedlands, Perth, Western Australia; 3 Ciba Vision, Basel, Switzerland; and the 4 University Eye Clinic, Strasbourg, France.
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 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
(10-10–10-4 M) of
either the docosanoid unoprostone isopropyl and its free acid or of
selected prostanoids: prostaglandin (PG) F2
and
thromboxane 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,
PGF2 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, PGF2
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 arterioles. Members of the prostanoid family demonstrated a different effect on the diameter of isolated retinal arterioles compared with the docosanoids. The potential therefore exists for the docosanoid unoprostone to have a beneficial effect on retinal blood flow in addition to any reduction in intraocular pressure.
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