In vivo effect of 8-epi-PGF2alpha on retinal circulation in diabetic and non-diabetic rats.
Retinal hemodynamic responses to a F2-isoprostane, 8-epi-PGF2alpha, were quantitated in vivo in non-diabetic and diabetic rats using a video fluorescein angiography system. Vascular diameters and retinal mean circulation time were determined before and after 5 microl intra-vitreous injection of 8-epi-PGF2alpha (10(-5) to 10(-3) M), 10(-4) M 8-epi-PGF2alpha, + 10(-3) M SQ29,548 or 10(-3) M LCB2853 (two inhibitors of TXA2 receptor), 10(4) M 9beta-PGF2alpha, or the carrier in non-diabetic animals. Diabetic rats received either 8-epi-PGF2alpha 10(-4) M, or the carrier. Compared to control animals, diabetic rats presented in the basal state a venous vasodilation (P<0.01), without modification of retinal mean circulation time or blood flow. After intravitreous injection of 8-epi-PGF2alpha, a significant arterial vasoconstriction was observed in control but not in diabetic animals. This vasoconstriction was concomitant with increased retinal mean circulation time in control but not in diabetic rats, inducing an impaired reduction of blood flow. No vasoconstriction was observed after injection of either the carrier, 9beta-PGF2alpha or the isoprostane associated to the inhibitors of TXA2 receptors. This is the first direct observation that the isoprostane 8-iso-PGF2alpha is a potent vasoconstricting agent in the retina. It occurs at the arterial but not venous level, and is likely mediated through a TXA2-like receptor. Differences observed between control and diabetic animals suggest altered adaptative mechanisms toward vasoconstrictor substances (such as isoprostanes) in diabetic rats.
Michoud
E
E
Diabetic Microangiopathy Research Unit, LIPHA-INSERM U352, INSA-Lyon, Villeurbanne, France. michoud@insa-lyon.fr
Lecomte
M
M
Lagarde
M
M
Wiernsperger
N
N
D000792:Angiography; D000818:Animals; D001783:Blood Flow Velocity; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D012171:Retinal Vessels / Q000033:anatomy & histology / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010648:Phenylacetates; D011463:Prostaglandins H; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; C091835:LCB 2853; C075750:8-epi-prostaglandin F2alpha; D044262:Prostaglandin H2; C045749:SQ 29548; D015237:Dinoprost