Captopril improves retinal neovascularization via endothelin-1

PURPOSE. The purpose of this study was to determine the effect of an angiot ensin converting ena me inhibitor, captopril, on oxygen-induced retinopathy (OIR) in the mouse. Endothelin-1 (ET-1) expression is assessed in a mouse model of OIR. METHODS. OIR was produced in C57BL6 mice. Captopril (0.5mg/kg/d SC) was giv en from P7 (post natal day 7) for 5 days. Retinopathy was assessed by a ret inal scoring system and by quantification of extra retinal neovascular nucl ei on retinal sections at P17 to P20. The expression of ET-1 was determined using a reverse transcriptase polymerase chain reaction. RESULTS. Pups treated with captopril during hyperoxia had a lower median re tinopathy score of 4.5 (25th, 75th quartile: 3, 6.4) compared with animals exposed to hyperoxia alone with median score 9.5 (25th, 75th quartile: 7.1, 10.4; P < 0.001). The pups treated with captopril during hyperoxia had sig nificant reduction in number of nuclei extending beyond the inner limiting membrane (15.8 +/- 16.7, mean +/- SD) when compared with the animals expose d to hyperoxia only (50.4 +/- 28.0; P < 0.01). ET-1 expression in the retin a increased 4.1-fold from P7 to P12 and a 1.9-fold increase from P12 to P17 . Overall, there was an 8-fold increase in ET-1 expression from P7 to P17. Hyperoxia increased ET-1 expression by 2.1-fold at P12 over room air-reared animals. At P17, there was a 2.9-fold increase in retinal ET-1 expression when compared with room air. At P17, there was a 6.2-fold suppression in ET -1 expression in captopril-treated animals when compared with the oxygen on ly-treated animals. CONCLUSIONS. Captopril reduces retinal neovascularization in a mouse model of oxygen-induced retinopathy. ET-1 expression is increased from P7 to P17, altered by hyperoxic exposure and relative hypoxic recovery and modulated by captopril in a mouse model of OIR.