Vascular dysfunction in ocular blood flow regulation impact of reactive oxygen species in an experimental setup

PURPOSE: 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.