Effects of systemic NO synthase inhibition on choroidal and optic nerve head blood flow in healthy subjects

Purpose. There is evidence from animal studies that nitric oxide (NO) is a major determinant of ocular blood flow. In humans NO synthase inhibition reduces pulsatile choroidal blood flow, but no data on optic nerve head (ONH) vasculature are available yet. The goal of this study was to investigate the effects of NO synthase inhibition on human choroidal and ONH blood flow using laser Doppler flowmetry. Methods. The study design was a randomized, placebo-controlled, double-masked, balanced threeway crossover. On separate study days 12 healthy male subjects received infusions of N(G)-nitro-Larginine (L-NMMA; either 3 mg/kg over 5 minutes followed by 30 μg/kg per minute over 55 minutes or 6 mg/kg over 5 minutes followed by 60 μg/kg per minute over 55 minutes) or placebo. The effects of L-NMMA or placebo on choroidal and ONH blood flow were measured with laser Doppler flowmetry. In addition, laser interferometric measurement of fundus pulsation was performed in the macula to assess pulsatile choroidal blood flow. Results. L-NMMA reduced all outcome parameters in the choroid and the ONH. The higher dose of L-NMMA caused a significant decrease in blood flow in the choroid (-26% ± 9%; P < 0.001) and the ONH (-20% ± 16%; P < 0.001) as evidenced from laser Doppler flowmetry and a significant decrease in fundus pulsation amplitude (-26% ± 5%; P < 0.001). Conclusions. These results indicate that NO is continuously released in human choroidal and ONH vessels.