title: The vasodilating effects of insulin and lactate are increased in precapillary arterioles in the porcine retina ex vivo.
abstract: OBJECTIVE
  Disturbances in the diameter regulation of the larger retinal vessels are involved in the pathophysiology of a number of vision threatening retinal diseases, but the role of the smaller vessels has received less attention. Therefore, an experimental model was developed for studying diameter changes in retinal vessels at all branching levels secondary to pharmacological interventions ex vivo.
  
  
  METHODS
  Porcine hemiretinas were mounted in a tissue chamber that allowed the control of temperature, pH and oxygen saturation. The chamber was positioned in a fluorescence microscope, and changes in the diameter of larger arterioles, precapillary arterioles and capillaries were studied after intravascular and extravascular application of the thromboxane analogue U46619, lactate, the glutamate agonist N-Methyl-D-aspartic acid (NMDA) and insulin.
  
  
  RESULTS
  U46619 induced significant contraction of all vessel calibres after extravascular application, but had no significant effect on vessel diameters after intravascular application. In contracted vessels, lactate induced significant dilatation in all vessel calibres, and the effect was more pronounced after intravascular than after extravascular application where only precapillary arterioles dilated significantly. N-Methyl-D-aspartic acid (NMDA) induced similar dilatation in the three vessel types after intra- and extravascular application, whereas the dilating effect of insulin was significantly more pronounced in the precapillary arterioles than in the other vessel types.
  
  
  CONCLUSIONS
  The diameter regulation in precapillary retinal arterioles differs from that of other retinal vascular branching levels and may play a special role in the pathophysiology of retinal vascular disease.
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Skov Jensen
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Metz Mariendal Pedersen
authors.affiliation: Department of Biomedicine (Physiology), University of Aarhus, Aarhus C, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Aalkjaer
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Toke
authors.initials: T
authors.lastname: Bek
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology*; D002196:Capillaries / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology; D012161:Retinal Artery / Q000502:physiology*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D007328:Insulin; D007773:Lactates; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D016202:N-Methylaspartate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
keywords: NMDA; diameter regulation; ex vivo model; insulin; lactate; perfused retina