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E. Mendrinos, I. K. Petropoulos, G. F. Mangioris, D. N. Papadopoulou, A. N. Stangos, N. Gilodi, C. J. Pournaras; Lactate-Induced Retinal Vasodilation Implicates Neuronal Nitric Oxide in Minipigs. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5371. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of neuronal nitric oxide (NO) in the retinal vasodilatory response to lactate in minipigs.
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
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.
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.
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