Lactate‐induced retinal vasodilation implicates neuronal nitric oxide synthesis in minipigs

Abstract

Abstract Purpose To investigate the role of neuronal nitric oxide (NO) synthesis in the retinal vasodilatory response to lactate in minipigs Methods Ten eyes of 10 minipigs were evaluated.After 1 hour of intravenous infusion of Nω‐nitro‐L‐arginine methylester (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 0.01 mol/l (pH= 7.4) was performed in all eyes but one which received balanced saline solution (BSS).Retinal arteriolar diameter changes were measured in vivo using a Retinal Vessel Analyzer.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 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 22.7% and 28.7% at 5 and 10 minutes respectively(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 Conclusion Juxta‐arteriolar administration of L‐lactate induced vasodilation despite inhibition of endothelial‐derived NO by the 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 the lactate‐induced vasodilation in minipigs