Influence of oxygen free radicals on the tone of ciliary arteries: a model of vasospasms of ocular vasculature.
BACKGROUND
Altered regulation of vascular tone and particularly vasospasms are thought to be a risk factor for the progression of primary open angle glaucoma (POAG). Apoptosis of retinal ganglion cells and possibly vascular tone regulation in glaucoma might be caused by oxidative stress. The aim of the present study was to investigate the influence of oxygen free radicals on the tone of ciliary arteries.


METHODS
The experiments were carried out with fresh ring preparations from porcine ciliary arteries obtained from a slaughterhouse. The preparations were placed in a self-designed myograph system and were kept under physiologic conditions (pH 7.4, 37 degrees C, Krebs-Henseleit-Buffer, 1.75 mM Ca(2+)). The muscles were sub-maximally activated by depolarization to -41 mV Nernst potential for K(+). The pre-activated preparations were exposed to hydroxyl radicals generated by the Fenton reaction (4 mM H(2)O(2); 30 microM Fe(3+)). Exposure time varied between 10 s and 60 s in order to obtain different radical-time-doses. The developed force was evaluated relatively to the developed force at maximal depolarization to -4 mV.


RESULTS
Ten seconds of radical exposure result in an additional increase of the relative developed force from 0.35 +/- .08 to 0.62 +/- 0.12 (P = 0.003; n = 8). Comparable results were obtained for 20 s and 60 s radical exposures. The developed force of a maximal activation to -4 mV was not reduced after a 10 s radical exposure (0.84 +/- 0.13; P = 0.25; n = 5), but was significantly reduced after 20 s exposure (0.25 +/- 0.21; P = 0.005; n = 6) and was virtually 0 after 60 s exposure.


CONCLUSIONS
The data shows that oxygen free radicals induce transient contractions of isolated ciliary artery rings. The shape of these contractions shows parallels to vasospasms. Thus the established system may serve as an in vitro model of vasospasms.
Zeitz
Oliver
O
Klinik und Poliklinik für Augenheilkunde, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. zeitz@uke.uni-hamburg.de
Wagenfeld
Lars
L
Wirtz
Nick
N
Galambos
Peter
P
Matthiesen
Natalya
N
Wiermann
Anne
A
Richard
Gisbert
G
Klemm
Maren
M
D000818:Animals; D019842:Ciliary Arteries / Q000502:physiology*; D005902:Glaucoma, Open-Angle / Q000503:physiopathology; D017665:Hydroxyl Radical / Q000494:pharmacology; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D018384:Oxidative Stress; D011188:Potassium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D011188:Potassium