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Originally published In Press as doi:10.1167/iovs.08-2087 on July 3, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:5060-5066.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-2087
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Lactate-Induced Retinal Arteriolar Vasodilation Implicates Neuronal Nitric Oxide Synthesis in Minipigs

Efstratios Mendrinos, Ioannis K. Petropoulos, Georgios Mangioris, Domniki N. Papadopoulou, Alexandros N. Stangos, and Constantin J. Pournaras

From the Laboratory of Ocular Vascular Diseases, Vitreo-retinal Unit, Department of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland.

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

METHODS. Thirteen eyes of 13 minipigs were evaluated. Ten eyes received an intravenous infusion of N{omega}-nitro-L-arginine methyl ester (L-NAME). After 1 hour, the same eyes received an intravitreous juxta-arteriolar microinjection of 30 µL of L-lactate 0.5 M (pH 7.4) through a micropipette. Ten minutes later, 9 of 10 eyes received an intravitreous juxta-arteriolar microinjection of 30 µL of L-NAME 0.01 M (pH 7.4), and 1 received physiologic saline solution (PSS). The remaining three eyes received a microinjection of 30 µL of L-lactate 0.5 M (pH 7.4), without intravenous or intravitreous L-NAME.

RESULTS. The three eyes that received juxta-arteriolar injection of L-lactate only showed a reproducible increase in retinal arteriolar diameter that persisted during the entire study period (maximum effect at 20 minutes, 40.9% ± 3.2%). Retinal arteriolar diameter decreased by 4.1% 1 hour after intravenous L-NAME when compared with baseline but the difference did not reach significance. The juxta-arteriolar injection of L-lactate induced a significant increase in retinal arteriolar diameter (22.7% and 28.7% at 5 and 10 minutes, respectively; P < 0.01), followed by a significant decrease (8.6%; P < 0.01) 10 minutes after juxta-arteriolar injection of L-NAME. Injection of PSS had no effect on retinal arteriolar diameter.

CONCLUSIONS. Juxta-arteriolar administration of L-lactate induced vasodilation, which was also observed with continuous intravenous infusion of L-NAME. Moreover, juxta-arteriolar L-NAME microinjection significantly suppressed the vasodilatory effect of L-lactate. These data suggest that neuronal-derived NO is an important mediator of lactate-induced vasodilation in minipigs.






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