Acute retinal ischemia inhibits endothelium-dependent nitric oxide-mediated dilation of retinal arterioles via enhanced superoxide production.

Abstract

PURPOSE:

Because retinal vascular disease is associated with ischemia and increased oxidative stress, the vasodilator function of retinal arterioles was examined after retinal ischemia induced by elevated intraocular pressure (IOP). The role of superoxide anions in the development of vascular dysfunction was assessed.

METHODS:

IOP was increased and maintained at 80 to 90 mm Hg for 30, 60, or 90 minutes by infusing saline into the anterior chamber of a porcine eye. The fellow eye with normal IOP (10-20 mm Hg) served as control. In some pigs, superoxide dismutase mimetic TEMPOL (1 mM) or vehicle (saline) was injected intravitreally before IOP elevation. After enucleation, retinal arterioles were isolated and pressurized without flow for functional analysis by recording diameter changes using videomicroscopic techniques. Dihydroethidium (DHE) was used to detect superoxide production in isolated retinal arterioles.

RESULTS:

Isolated retinal arterioles developed stable basal tone and the vasodilations to endothelium-dependent nitric oxide (NO)-mediated agonists bradykinin and L-lactate were significantly reduced only by 90 minutes of ischemia. However, vasodilation to endothelium-independent NO donor sodium nitroprusside was unaffected after all time periods of ischemia. DHE staining showed that 90 minutes of ischemia significantly increased superoxide levels in retinal arterioles. Intravitreal injection of membrane-permeable radical scavenger but not vehicle before ischemia prevented elevation of vascular superoxide and preserved bradykinin-induced dilation.

CONCLUSIONS:

Endothelium-dependent NO-mediated dilation of retinal arterioles is impaired by 90 minutes of ischemia induced by elevated IOP. The inhibitory effect appears to be mediated by the alteration of NO signaling via vascular superoxide.

• Authors: Travis W Hein, Yi Ren, Luke B Potts, Zhaoxu Yuan, Enoch Kuo, Robert H Rosa Jr, Lih Kuo
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 53 Issue 1 Pg. 30-6 (Jan 03 2012) ISSN: 1552-5783 [Electronic] United States
• PMID: 22110081 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic N-Oxides
• Spin Labels
• Superoxides
• Nitroprusside
• Nitric Oxide
• Nitric Oxide Synthase Type III
• Bradykinin
• tempol

Topics

• Acute Disease
• Animals
• Arterioles (metabolism)
• Bradykinin (pharmacology)
• Cyclic N-Oxides (administration & dosage)
• Endothelium, Vascular (metabolism)
• Female
• Intraocular Pressure
• Male
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Nitroprusside (pharmacology)
• Ocular Hypertension (metabolism)
• Reperfusion Injury (metabolism)
• Retinal Artery (metabolism)
• Spin Labels
• Superoxides (metabolism)
• Swine
• Vasodilation (physiology)