title: Vascular dysfunction in ocular blood flow regulation: impact of reactive oxygen species in an experimental setup.
abstract: OBJECTIVE
  Glaucoma is associated with an altered blood flow and increased levels of reactive oxygen species (ROS). Reactive oxygen species can have opposing influences on the tone of a vessel; depending on the condition and type of the vessel, ROS can induce vasodilation or vasoconstriction. In the present study, we investigated the impact of ROS on the tone of rat ophthalmic arteries under various conditions and present data on the underlying mechanisms.
  
  
  METHODS
  Freshly dissected rat ophthalmic arteries were pressurized in a perfusion setup to 80 mm Hg, at which a stable myogenic tone was observed. After various pretreatments (e.g., removal of endothelium, partial depolarization to -41 mV, blocking of the Na(+)/Ca(2+)-exchanger (NCX) in reverse mode by KB-R7943, or blocking of the Na(+)/K(+)-ATPase by ouabain), the vessels were exposed to ROS. Vessel diameter was continuously recorded and values before and after treatment compared.
  
  
  RESULTS
  Stable myogenic tone of vessels with and without endothelium was established at a pressure of 80 mm Hg. At the physiological resting membrane potential, ROS exposure led to a significant vasodilatation, which was significantly reduced by pretreatment with ouabain. After depolarization to -41 mV, ROS exposure led to vasoconstriction. Blocking the NCX in reverse mode using KB-R7943 completely abolished this ROS-induced vasoconstriction.
  
  
  CONCLUSIONS
  At resting potential, ROS provoke dilation; however, in precontracted vessels they act synergistically and induce further vasoconstriction. In diseases involving altered blood flow through altered vascular tone (e.g., vasospasms), ROS may influence blood flow and may thereby contribute indirectly to further disease progression.
authors.affiliation: University Medical Center Hamburg-Eppendorf, Department of Ophthalmology, Hamburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Wagenfeld
authors.affiliation: University Medical Center Hamburg-Eppendorf, Department of Ophthalmology, Hamburg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Weiss
authors.affiliation: University Medical Center Hamburg-Eppendorf, Department of Ophthalmology, Hamburg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Klemm
authors.affiliation: University Medical Center Hamburg-Eppendorf, Department of Ophthalmology, Hamburg, Germany.
authors.forename: Gisbert
authors.initials: G
authors.lastname: Richard
authors.affiliation: University Medical Center Hamburg-Eppendorf, Department of Ophthalmology, Hamburg, Germany Global Clinical Development Ophthalmology, Bayer Pharma AG, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zeitz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004108:Dilatation, Pathologic / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009880:Ophthalmic Artery / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000633:toxicity*; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D017382:Reactive Oxygen Species
keywords: glaucoma; myogenic tone; oxygen free radicals; reactive oxygen species; vascular dysfunction