Abstract

P 006

Vascular dysfunction: Endothel depending effect of oxygen free radicals on the vascular tone

Ralf Praga, Oliver Zeitz, S. Weiß, Maren Klemm, Peter Galambos, Claudia Rebel, Gisbert Richard, Lars Wagenfeld
Klinik und Poliklinik für Augenheilkunde, Universitätsklinikum Hamburg-Eppendorf, Hamburg

Objective
Oxygen free radicals are involved in various physiological and aging processes. A backlog at cellular level is engaged in the pathogenesis of various ocular diseases like ARMD, diabetic retnopathy or glaucoma by influencing microcirculation. Various effects on vasculature are reported for oxygen free radicals. These effects vary between dilation and constriction. Aim of the presented study was to describe potential mechanisms of these effects and to describe the conditions oxygen free radicals could influence ocular circulation negatively.
Methods
Our experiments were carried out with perfused rat ophthalmic arteries that were pressurized in steps of 10 mmHg up to 80 mmHg. After a reproducible myogenic tone with stabilized vascular diameters was established a 20s lasting exposition of hydroxyl radicals (OH.) generatetd by Fenton reaction was performed. Previously a part of the preparations was deendothelized using triton. In one fraction of experiments Nernst membrane potential for K+ was adjusted at 88mV (equivalent to physiological 5mM [K+]e) in another fraction to 41mV. . Changes of diameters before and after exposing with radicals were compared using paired or unpaired student t-tests.
Results
Our vessels show a stable and reproducible myogenic tone at 80 mmHg. At a physiological membrane potential an OH, exposure leads to a significant dilation (252.7±3.2 µm before OH. vs. 289.1±2.6 µm after OH.; P<0.001; n=14). without endothel: 216,4±0,7 µm before OH vs. 253,7±1,4 µm after OH; P=0,003; n=8). Vessels that are partially depolarized to -41mV constrict after oxygen free radical exposure (199.4 ± 1.7 µm vs. 183.1 ±1.5 µm; P<0.001; n=10; without endothel: 174,5±3,9 µm vs. 163,2±4,1 µm; P=0,006; n=6). A sole treatment with Fe3+ (sham-exposition) had no effects on diameter of the vessels. After OH, exposure complete depolarization provoked a further significant vasoconstriction in all goups (P<0,001 bzw. P=0,002).
Conclusions
Recognized vasomotor effects depeding on membranepotential are autonomous from the presence of vascular endothel. Concluding, it can therefore be stated that free radicals directly affect the muscular tonicity of vessels and influence regulation of microperfusion. Thus they are involved in the pathogenesis of several ocular diseases.

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