Abstract 405 Development Pharmacology: Drug Effects on Neonatal Angiogenesis and Vascular Function Platform, Monday, 5/3

PURPOSE: Captopril is a pharmacological agent that inhibits angiotensin converting enzyme (ACE). ACE stimulates the production of endothelin-1 (ET-1), a potent vasoconstrictor, by converting angiotensin I to angiotensin II and subsequently increasing intracellular calcium. ET-1 has been implicated in hyperoxic retinal vasoconstriction in vitro and in vivo. This experiment was performed to determine the effect of the ACE inhibitor, captopril, on oxygen induced retinopathy. METHODS: Oxygen induced retinopathy was produced in mice by exposing them to 75% oxygen from postnatal age 7 (P7) through postnatal age 12 (P12). The animals were divided into four groups: a control group, a control group exposed to captopril at a dose of 0.5 mg/kg/day subcutaneously from P7 for five days, a group exposed to oxygen, and a group to oxygen and captopril at a dose of 0.5 mg/kg/day from P7 for five days. All the animals were sacrificed at P17- P21. Retinopathy was assessed by a previously validated retinopathy scoring system evaluation of retinate from animals perfused with high molecular weight fluorescein conjugated dextran and by quantification of extra neovascular nuclei on retinal sections. Data were analyzed using the Kruskall Wallis test, Mann Whitney test, and student t test.

RESULTS: Captopril given during the injury phase of retinopathy improves retinal neovascularization. (Table) Retinopathy score is represented as median (25th, 75th quartile), neovascular nuclei are represented as mean ± standard deviation, and weights are expressed as mean ± standard deviation. Weight on the day of sacrifice was not affected by captopril or oxygen treatment. * denotes p< 0.05 when compared to oxygen only treatment.

Table 1 No caption available
Full size table

CONCLUSION: Captopril improves retinal neovascularization in a mouse model of oxygen induced retinopathy without having adverse effects on the general health of the animals or in retinal vascular development. We speculate that captopril decrease neovascularization indirectly by inhibiting vasoconstriction via ET-1.

Funded by Knights Templar Eye Foundation.