Lactate-Induced Retinal Vasodilation Implicates Neuronal Nitric Oxide in Minipigs

Abstract

Purpose: : To investigate the role of neuronal nitric oxide (NO) in the retinal vasodilatory response to lactate in minipigs.

Methods: : Under general anesthesia, 10 eyes of 10 minipigs were evaluated. All animals received an intravenous infusion of nitro-L-arginine methyl ester (L-NAME) (bolus of 6mg/kg over 5min followed by continuous infusion of 60 µg/kg/min during the entire study period). After 1 hour of intravenous infusion of L-NAME, an intravitreal juxta-arteriolar microinjection of 30µl of L-lactate 0.5 mol/l (pH= 7.4) was performed through a micropipette. Ten minutes later, an intravitreal juxta-arteriolar microinjection of 30µl of L-NAME 0.1 mol/l (pH= 7.4) was performed in all eyes but one which received balanced saline solution (BSS). The procedure was recorded in real time and retinal arteriolar diameter changes were measured in vivo using a Retinal Vessel Analyzer. Throughout the experiments, the animals’ vital signs were monitored and systemic arterial pressure was maintained stable

Results: : Retinal arteriolar diameter decreased by 4.1% 1 hour after intravenous L-NAME infusion when compared to baseline but the difference did not reach significance. Juxta-arteriolar injection of L-lactate induced a significant increase in retinal arteriolar diameter of 28.7% at 10 min (p<0.01). This was followed by a significant decrease of 8.6% 10 min after juxta-arteriolar injection of L-NAME (p<0.01). Injection of BBS had no effect in the control eye and retinal arterioles remained dilated under the effect of L-lactate.

Conclusions: : Juxta-arteriolar administration of L-lactate induced vasodilation despite inhibition of endothelial NO by the continuous intravenous L-NAME infusion. Moreover, juxta-arteriolar L-NAME microinjection, which is expected to inhibit predominantly neuronal NO synthase in retinal glial cells surrounding the arteriolar wall, significantly suppressed the vasodilatory effect of L-lactate. These data suggest that neuronal NO is an important mediator of the lactate-induced vasodilation in minipigs.

Keywords: nitric oxide