The effect of systemic nitric oxide-synthase inhibition on ocular fundus pulsations in man

There is experimental evidence that endothelium derived nitric oxide is involved in the regulation of ocular vascular tone. The purpose of this study was to investigate the effects of NO-synthase inhibition by N-monomethyl-L-arginine (L-NMMA) on ocular fundus pulsations in young healthy volunteers. Three milligrams per kilograms L-NMMA were administered i.v. over 5 minutes. Protocol 1: Measurements of blood pressure, pulse rate, fundus pulsation amplitude, NO-exhalation, and cardiac output were performed at baseline and 10, 30, 60, 90, 150, and 300 minutes after L-NMMA infusion (n = 8). Fundus pulsation amplitude, which has been shown to estimate the pulsatile component of the choroidal blood flow, was recorded with a recently developed laser interferometer. Protocol 2: Measurements of blood pressure, pulse rate, fundus pulsation amplitude, NO-exhalation, and blood flow velocity in the ophthalmic artery were performed in a randomized, placebo controlled cross over study (n = 10). Ten minutes after L-NMMA administration fundus pulsation amplitude decreased by 23 +/- 2% (protocol 1) and 19 +/- 1% (protocol 2, P < 0.01 each), cardiac output by 12 +/- 2% (P < 0.01), and exhaled NO by 55 +/- 6% (protocol 1) and 41 +/- 6% (protocol 2, P < 0.01 each). All parameters returned to baseline values within the 300 minutes observation period, with a faster recovery of fundus pulsation amplitude than of cardiac output and exhaled NO. Blood pressure, pulse rate, and ophthalmic artery blood flow velocity showed only minor changes during and after administration of L-NMMA. Our results suggest that systemic NO-synthase inhibition reduces pulsatile choroidal and most likely total choroidal blood flow in humans. The recovery of vascular tone in choroidal vessels seems to be different from the cardiovascular response. Our findings indicate that reduced fundus pulsations after L-NMMA are caused by systemic factors as well as by local reactions of the choroidal vasculature.