Effect of nitric oxide on anterior segment physiology in monkeys

Invest Ophthalmol Vis Sci. 2013 Jul 30;54(7):5103-10. doi: 10.1167/iovs.12-11491.

Abstract

Purpose: To determine the effect of the nitric oxide donor, sodium nitroprusside (SNP), and the nitric oxide synthase (NOS) inhibitor, L-nitro-arginine-methylester (L-NAME), on IOP, mean arterial pressure (MAP), pupil diameter (PD), refraction (Rfx), aqueous humor formation (AHF), and outflow facility (OF) in monkeys.

Methods: Monkeys were treated with single or multiple topical treatments of 500 μg SNP or L-NAME to one eye. IOP was determined by Goldmann applanation tonometry, PD with vernier calipers in room light, Rfx by Hartinger coincidence refractometry, AHF by fluorophotometry, and MAP with a blood pressure monitor. OF was determined by two-level constant pressure perfusion following anterior chamber exchange.

Results: Following four topical treatments with 500 μg SNP, 30 minutes apart, IOP was significantly decreased from 2 to 6 hours compared with the contralateral control with the maximum IOP reduction of 20% at 3 hours (P < 0.001). PD, Rfx, and AHF were unchanged. Effects on MAP were variable. OF after SNP exchange was significantly increased by 77% (P < 0.05) at 10(-3) M. Topical L-NAME had no effect on IOP, PD, Rfx, or MAP.

Conclusions: Enhancement of nitric oxide concentration at targeted tissues in the anterior segment may be a useful approach for IOP reduction for glaucoma therapy. Additional studies are warranted before conclusions can be made regarding the effect of NOS inhibition on ocular physiology in nonhuman primates.

Keywords: intraocular pressure; nitric oxide; outflow facility.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Anterior Eye Segment / drug effects*
  • Anterior Eye Segment / physiology
  • Aqueous Humor / drug effects
  • Blood Pressure / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Heart Rate / drug effects
  • Intraocular Pressure / drug effects
  • Macaca fascicularis / physiology*
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / physiology*
  • Nitric Oxide Donors / pharmacology*
  • Nitroprusside / pharmacology*
  • Pupil / drug effects
  • Refraction, Ocular / drug effects

Substances

  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • Nitroprusside
  • Nitric Oxide
  • NG-Nitroarginine Methyl Ester