Captopril improves retinal neovascularization via endothelin-1.
OBJECTIVE
The purpose of this study was to determine the effect of an angiotensin converting enzyme 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 given from P7 (post natal day 7) for 5 days. Retinopathy was assessed by a retinal scoring system and by quantification of extra retinal neovascular nuclei 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 retinopathy 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 significant reduction in number of nuclei extending beyond the inner limiting membrane (15.8 +/- 16.7, mean +/- SD) when compared with the animals exposed to hyperoxia only (50.4 +/- 28.0; P < 0.01). ET-1 expression in the retina 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 only-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.
Tadesse
M
M
Georgetown University Children's Medical Center, Department of Pediatrics, Division of Neonatology, 3800 Reservoir Road NW, Washington, DC 20007, USA.
Yan
Y
Y
Yossuck
P
P
Higgins
R D
RD
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D003911:Dextrans / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D005451:Fluorescein Angiography; D005452:Fluoresceins / Q000378:metabolism; D005654:Fundus Oculi; D018496:Hyperoxia / Q000150:complications; D051379:Mice; D008810:Mice, Inbred C57BL; D010477:Perfusion; D012333:RNA, Messenger / Q000096:biosynthesis; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000806:Angiotensin-Converting Enzyme Inhibitors; D003911:Dextrans; D019332:Endothelin-1; D005452:Fluoresceins; D012333:RNA, Messenger; C052526:fluorescein-dextran; D002216:Captopril