Comparison of the vasoactive effects of the docosanoid unoprostone and selected prostanoids on isolated perfused retinal arterioles.
OBJECTIVE
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) F(2alpha) and thromboxane A(2) 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, PGF(2alpha) 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, PGF(2alpha) 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.
Yu
D Y
DY
Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth. dyyu@cyllene.uwa.edu.au
Su
E N
EN
Cringle
S J
SJ
Schoch
C
C
Percicot
C P
CP
Lambrou
G N
GN
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010477:Perfusion; D012161:Retinal Artery / Q000187:drug effects*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C072630:isopropyl unoprostone; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost