Abstract

P 010

Vascular dysfunction: Effects of oxygen free radicals on vascular muscle cells

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

Objective
Oxygen free radicals are involved in various physiological and aging processes. An overhang on cellular basis 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 constriction. Aim of the presented study was to describe potential mechanisms of thes effects and to describe for which circumstances 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 was established a pharmacological treatment with Ouabain - a blocker of the Na-K ATPase - or KBR7403 (blocker of NCX) was done These vessels were exposed to oxygen free radicals from the fenton reaction . The diameter of the vessel was continuously recorded by a digital edge-detection system. Changes of diameters 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). This dilation can be blocked by oubain (223.1±3.2 µm vs. 227.0 ± 3.2 µm, p=0.19, n=13) Percental dilation is reduced by oubain: 3.0 ± 2.4 % (with oubain) vs. 15.5 ± 1.8 % (without oubain); p=0.01, n=11. 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). This constriction can be reduced by KBR7403: 227.7 ± 2.0 µm before OH.  vs. 222.8 ± 2.7 µm after OH; p=0.98; n=14. Percental changes show a significant difference: -0.31 ± 13.4 % (with KBR7403) vs. -7.7 ± % (without KBR7403); P=0.009; n=12.
Conclusions
Oxygen free radicals can lead to hyperpolarization of smooth muscle cells by activation of the Na-K-ATPase. If a damage and eventually a partial depolarization is present, another mechanism is dominant: radicals influence the Na-Ca-exchanger and lead to a constriction of the vessel. Radicals could therefore appear secondary, at pre-damaged vessels they also could potentiate the damage.

Copyright: 2009 Porstmann Kongresse GmbH. All rights reserved. Impressum, Disclaimer.