Acute retinal ischemia inhibits endothelium‐dependent nitric oxide‐mediated dilation of retinal arterioles: role of endothelin‐1 and superoxide

Abstract

Increases in endothelin‐1 (ET‐1) and oxidative stress are associated with retinal vascular disease. Herein, we assessed whether acute retinal ischemia increases local ET‐1 and superoxide (O2−), and alters nitric oxide (NO)‐mediated dilation of retinal arterioles. Retinal ischemia was established by elevating intraocular pressure (IOP) to 90 mmHg for 30 or 90 min via infusion of saline into the anterior chamber of the porcine eye. Following ischemia, retinal arterioles from control and ischemic eyes were isolated and pressurized without flow for in vitro study. Dilation to endothelium‐dependent NO‐mediated agonist bradykinin but not endothelium‐independent NO donor nitroprusside was significantly reduced in arterioles following only 90‐min ischemia. Dihydroethidium staining and ET‐1 ELISA revealed increase of O2− inarterioles and ET‐1 in the vitreous after ischemia. Pre‐ischemia intravitreal treatment with O2− scavenger TEMPOL or ET‐converting enzyme inhibitor phosphoramidon prevented elevation of O2− and preserved dilation to bradykinin. Phosphoramidon but not TEMPOL reduced vitreous ET‐1. Our data show that acute retinal ischemia inhibits endothelium‐dependent NO‐mediated dilation of retinal arterioles. The impairment is mediated by elevation of local ET‐l and subsequent NO inactivation via increased vascular O2−. Support: Retina Research Foundation and Scott & White Research Foundation.