THE IN-VIVO EFFECT OF ENDOTHELINS ON RETINAL CIRCULATION IN NONDIABETIC AND DIABETIC RATS

Purpose. The endothelins are potent vasoactive peptides. This study wa s performed to characterize the in vivo effects of the endothelin pept ides on the retinal circulation in nondiabetic and diabetic rats. Meth ods. The video fluorescein angiography methodology was used to quantit ate retinal hemodynamic responses to endothelin-1 (ET-1) and endotheli n-3 (ET-3) in rats. A total of 99 rats were used for these experiments . Video fluorescein angiography recordings were performed before and a t different times after intravitreal injection of different concentrat ions of ET-1 and ET-3 in nondiabetic and diabetic rats. Vascular diame ters and retinal circulation times were determined using computer-assi sted image analysis of the recorded angiograms. Results. The maximal r esponse to ET-1 was observed at 15 minutes after intravitreal injectio n and was maintained for as long as 30 minutes after injection. Subseq uent data measured at 15 minutes after intravitreal injection showed s ignificant prolongation of retinal circulation times and retinal arter y constriction. For example, at a concentration of 10(-7) M, the retin al circulation time increased by 270% +/- 121% of the baseline value. In contrast, 10(-7) M ET-3 injection showed a 52% +/- 29.5% increase i n circulation time compared to baseline. In diabetic animals, 10(-7) M ET-1 injection showed a blunted response (only 26% +/- 8% of baseline ) compared to the same ET-1 injected concentration in nondiabetic rats . Conclusions. The rat retinal circulation shows a pronounced retinal response to ET-1 intravitreal injection. The response to ET-3 is signi ficantly less than it is to ET-1, and in diabetic animals there was al so a significant blunting of the retinal response to ET-1. The blunted response to ET-3 is consistent with the lower affinity of retinal ves sel ET-1 receptors to ET-3. The blunted ET-1 response in diabetic rats is consistent with previously reported results, demonstrating resista nce to ET-1 action in retinal pericytes exposed to high glucose.