In vivo effect of 8-epi-PGF(2 alpha) on retinal circulation in diabetic and non-diabetic rats

Retinal hemodynamic responses to a F-2-isoprostane, 8-epi-PGF(2 alpha), wer e quantitated in vivo in non-diabetic and diabetic rats using a Video fluor escein angiography system. Vascular diameters and retinal mean circulation time were determined before and after 5 mu l intra-vitreous injection of 8- epi-PGF(2 alpha) (10(-5) to 10(-3) M), 10(-4) M 8-epi-PGF(2 alpha) + 10(-3) M SQ29,548 or 10(-3) M LCB2853 (two inhibitors of TXA(2) receptor), 10(-4) M 9 beta-PGF(2 alpha), or the carrier in non-diabetic animals. Diabetic ra ts received either 8-epi-PGF(2 alpha) 10(-4) M, or the carrier. Compared to control animals, diabetic rats presented in the basal state a venous vasod ilation (P<0.01), without modification of retinal mean circulation time or blood flow. After intravitreous injection of 8-epi-PGF(2 alpha), a signific ant arterial vasoconstriction was observed in control but not in diabetic a nimals. This vasoconstriction was concomitant with increased retinal mean c irculation time in control but not in diabetic rats, inducing an impaired r eduction of blood flow. No vasoconstriction was observed after injection of either the carrier, 9 beta-PGF(2 alpha) or the isoprostane associated to t he inhibitors of TXA(2) receptors. This is the first direct observation tha t the isoprostane 8-iso-PGF(2 alpha) is a potent vasoconstricting agent in the retina. It occurs at the arterial but not venous level, and is likely m ediated through a TXA(2)-like receptor. Differences observed between contro l and diabetic animals suggest altered adaptative mechanisms toward vasocon strictor substances (such as isoprostanes) in diabetic rats.