title: Lactate-induced retinal arteriolar vasodilation implicates neuronal nitric oxide synthesis in minipigs.
abstract: OBJECTIVE
  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 microL 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 microL 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 microL 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.
authors.affiliation: Department of Ophthalmology, Laboratory of Ocular Vascular Diseases, Vitreo-retinal Unit, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Mendrinos
authors.forename: Ioannis K
authors.initials: IK
authors.lastname: Petropoulos
authors.forename: Georgios
authors.initials: G
authors.lastname: Mangioris
authors.forename: Domniki N
authors.initials: DN
authors.lastname: Papadopoulou
authors.forename: Alexandros N
authors.initials: AN
authors.lastname: Stangos
authors.forename: Constantin J
authors.initials: CJ
authors.lastname: Pournaras
mesh_terms: D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000096:biosynthesis*; D012161:Retinal Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D014664:Vasodilation / Q000187:drug effects*; D014822:Vitreous Body
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester