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Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 9/2007

01-09-2007 | Laboratory Investigation

Influence of oxygen free radicals on the tone of ciliary arteries: a model of vasospasms of ocular vasculature

Authors: Oliver Zeitz, Lars Wagenfeld, Nick Wirtz, Peter Galambos, Natalya Matthiesen, Anne Wiermann, Gisbert Richard, Maren Klemm

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 9/2007

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Abstract

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°C, Krebs-Henseleit-Buffer, 1.75 mM Ca2+). 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 H2O2; 30 μM Fe3+). 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.

Discussion

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.
Literature
1.
go back to reference Aladag MA, Turkoz Y, Ozcan C, Sahna E, Parlakpinar H, Akpolat N, Cigremis Y (2006) Caffeic acid phenethyl ester (CAPE) attenuates cerebral vasospasm after experimental subarachnoidal haemorrhage by increasing brain nitric oxide levels. Int J Dev Neurosci 24:9–14PubMedCrossRef Aladag MA, Turkoz Y, Ozcan C, Sahna E, Parlakpinar H, Akpolat N, Cigremis Y (2006) Caffeic acid phenethyl ester (CAPE) attenuates cerebral vasospasm after experimental subarachnoidal haemorrhage by increasing brain nitric oxide levels. Int J Dev Neurosci 24:9–14PubMedCrossRef
2.
go back to reference Auch-Schwelk W, Katusic ZS, Vanhoutte PM (1989) Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat. Hypertension 13:859–864PubMed Auch-Schwelk W, Katusic ZS, Vanhoutte PM (1989) Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat. Hypertension 13:859–864PubMed
4.
go back to reference Clark JF, Sharp FR (2006) Bilirubin oxidation products (BOXes) and their role in cerebral vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab 26:1223–1233PubMedCrossRef Clark JF, Sharp FR (2006) Bilirubin oxidation products (BOXes) and their role in cerebral vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab 26:1223–1233PubMedCrossRef
5.
go back to reference Ferreira SM, Lerner SF, Brunzini R, Evelson PA, Llesuy SF (2004) Oxidative stress markers in aqueous humor of glaucoma patients. Am J Ophthalmol 137:62–69PubMedCrossRef Ferreira SM, Lerner SF, Brunzini R, Evelson PA, Llesuy SF (2004) Oxidative stress markers in aqueous humor of glaucoma patients. Am J Ophthalmol 137:62–69PubMedCrossRef
6.
go back to reference Flammer J, Orgul S, Costa VP, Orzalesi N, Krieglstein GK, Serra LM, Renard JP, Stefansson E (2002) The impact of ocular blood flow in glaucoma. Prog Retin Eye Res 21:359–393PubMedCrossRef Flammer J, Orgul S, Costa VP, Orzalesi N, Krieglstein GK, Serra LM, Renard JP, Stefansson E (2002) The impact of ocular blood flow in glaucoma. Prog Retin Eye Res 21:359–393PubMedCrossRef
7.
go back to reference Flammer J, Pache M, Resink T (2001) Vasospasm, its role in the pathogenesis of diseases with particular reference to the eye. Prog Retin Eye Res 20:319–349PubMedCrossRef Flammer J, Pache M, Resink T (2001) Vasospasm, its role in the pathogenesis of diseases with particular reference to the eye. Prog Retin Eye Res 20:319–349PubMedCrossRef
8.
go back to reference Galambos P, Vafiadis J, Vilchez SE, Wagenfeld L, Matthiessen ET, Richard G, Klemm M, Zeitz O (2006) Compromised autoregulatory control of ocular hemodynamics in glaucoma patients after postural change. Ophthalmology 113:1832–1836PubMedCrossRef Galambos P, Vafiadis J, Vilchez SE, Wagenfeld L, Matthiessen ET, Richard G, Klemm M, Zeitz O (2006) Compromised autoregulatory control of ocular hemodynamics in glaucoma patients after postural change. Ophthalmology 113:1832–1836PubMedCrossRef
9.
go back to reference Gherghel D, Griffiths HR, Hilton EJ, Cunliffe IA, Hosking SL (2005) Systemic reduction in glutathione levels occurs in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci 46:877–883PubMedCrossRef Gherghel D, Griffiths HR, Hilton EJ, Cunliffe IA, Hosking SL (2005) Systemic reduction in glutathione levels occurs in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci 46:877–883PubMedCrossRef
10.
go back to reference Gherghel D, Hosking SL, Cunliffe IA (2004) Abnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients: a case for autonomic failure? Invest Ophthalmol Vis Sci 45:3546–3554PubMedCrossRef Gherghel D, Hosking SL, Cunliffe IA (2004) Abnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients: a case for autonomic failure? Invest Ophthalmol Vis Sci 45:3546–3554PubMedCrossRef
11.
go back to reference Gugleta K, Orgul S, Hasler PW, Picornell T, Gherghel D, Flammer J (2003) Choroidal vascular reaction to hand-grip stress in subjects with vasospasm and its relevance in glaucoma. Invest Ophthalmol Vis Sci 44:1573–1580PubMedCrossRef Gugleta K, Orgul S, Hasler PW, Picornell T, Gherghel D, Flammer J (2003) Choroidal vascular reaction to hand-grip stress in subjects with vasospasm and its relevance in glaucoma. Invest Ophthalmol Vis Sci 44:1573–1580PubMedCrossRef
12.
go back to reference Janssen PM, Zeitz O, Hasenfuss G (1999) Transient and sustained impacts of hydroxyl radicals on sarcoplasmic reticulum function: protective effects of nebivolol. Eur J Pharmacol 366:223–232PubMedCrossRef Janssen PM, Zeitz O, Hasenfuss G (1999) Transient and sustained impacts of hydroxyl radicals on sarcoplasmic reticulum function: protective effects of nebivolol. Eur J Pharmacol 366:223–232PubMedCrossRef
13.
go back to reference Ko ML, Peng PH, Ma MC, Ritch R, Chen CF (2005) Dynamic changes in reactive oxygen species and antioxidant levels in retinas in experimental glaucoma. Free Radic Biol Med 39:365–373PubMedCrossRef Ko ML, Peng PH, Ma MC, Ritch R, Chen CF (2005) Dynamic changes in reactive oxygen species and antioxidant levels in retinas in experimental glaucoma. Free Radic Biol Med 39:365–373PubMedCrossRef
14.
go back to reference Moreno MC, Campanelli J, Sande P, Sanez DA, Keller Sarmiento MI, Rosenstein RE (2004) Retinal oxidative stress induced by high intraocular pressure. Free Radic Biol Med 37:803–812PubMedCrossRef Moreno MC, Campanelli J, Sande P, Sanez DA, Keller Sarmiento MI, Rosenstein RE (2004) Retinal oxidative stress induced by high intraocular pressure. Free Radic Biol Med 37:803–812PubMedCrossRef
15.
go back to reference Mulieri LA, Hasenfuss G, Ittleman F, Blanchard EM, Alpert NR (1989) Protection of human left ventricular myocardium from cutting injury with 2,3-butanedione monoxime. Circ Res 65:1441–1449PubMed Mulieri LA, Hasenfuss G, Ittleman F, Blanchard EM, Alpert NR (1989) Protection of human left ventricular myocardium from cutting injury with 2,3-butanedione monoxime. Circ Res 65:1441–1449PubMed
16.
go back to reference Neri S, Signorelli S, Pulvirenti D, Mauceri B, Cilio D, Bordonaro F, Abate G, Interlandi D, Misseri M, Ignaccolo L, Savastano M, Azzolina R, Grillo C, Messina A, Serra A, Tsami A (2006) Oxidative stress, nitric oxide, endothelial dysfunction and tinnitus. Free Radic Res 40:615–618PubMedCrossRef Neri S, Signorelli S, Pulvirenti D, Mauceri B, Cilio D, Bordonaro F, Abate G, Interlandi D, Misseri M, Ignaccolo L, Savastano M, Azzolina R, Grillo C, Messina A, Serra A, Tsami A (2006) Oxidative stress, nitric oxide, endothelial dysfunction and tinnitus. Free Radic Res 40:615–618PubMedCrossRef
17.
go back to reference Ray SK, Fidan M, Nowak MW, Wilford GG, Hogan EL, Banik NL (2000) Oxidative stress and Ca2+ influx upregulate calpain and induce apoptosis in PC12 cells. Brain Res 852:326–334PubMedCrossRef Ray SK, Fidan M, Nowak MW, Wilford GG, Hogan EL, Banik NL (2000) Oxidative stress and Ca2+ influx upregulate calpain and induce apoptosis in PC12 cells. Brain Res 852:326–334PubMedCrossRef
18.
go back to reference Rhoades RA, Packer CS, Roepke DA, Jin N, Meiss RA (1990) Reactive oxygen species alter contractile properties of pulmonary arterial smooth muscle. Can J Physiol Pharmacol 68:1581–1589PubMed Rhoades RA, Packer CS, Roepke DA, Jin N, Meiss RA (1990) Reactive oxygen species alter contractile properties of pulmonary arterial smooth muscle. Can J Physiol Pharmacol 68:1581–1589PubMed
19.
go back to reference Sacca SC, Pascotto A, Camicione P, Capris P, Izzotti A (2005) Oxidative DNA damage in the human trabecular meshwork: clinical correlation in patients with primary open-angle glaucoma. Arch Ophthalmol 123:458–463PubMedCrossRef Sacca SC, Pascotto A, Camicione P, Capris P, Izzotti A (2005) Oxidative DNA damage in the human trabecular meshwork: clinical correlation in patients with primary open-angle glaucoma. Arch Ophthalmol 123:458–463PubMedCrossRef
20.
go back to reference Tezel G (2006) Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog Retin Eye Res 25:490–513PubMedCrossRef Tezel G (2006) Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog Retin Eye Res 25:490–513PubMedCrossRef
21.
go back to reference Tutaj M, Brown CM, Brys M, Marthol H, Hecht MJ, Dutsch M, Michelson G, Hilz MJ (2004) Dynamic cerebral autoregulation is impaired in glaucoma. J Neurol Sci 220:49–54PubMedCrossRef Tutaj M, Brown CM, Brys M, Marthol H, Hecht MJ, Dutsch M, Michelson G, Hilz MJ (2004) Dynamic cerebral autoregulation is impaired in glaucoma. J Neurol Sci 220:49–54PubMedCrossRef
22.
go back to reference Veriac S, Tissie G, Bonne C (1993) Oxygen free radicals adversely affect the regulation of vascular tone by nitric oxide in the rabbit retina under high intraocular pressure. Exp Eye Res 56:85–88PubMedCrossRef Veriac S, Tissie G, Bonne C (1993) Oxygen free radicals adversely affect the regulation of vascular tone by nitric oxide in the rabbit retina under high intraocular pressure. Exp Eye Res 56:85–88PubMedCrossRef
23.
go back to reference Wiklund L, McGregor CG, Miller VM (1996) Effects of prolonged exposure to oxygen-derived free radicals in canine pulmonary arteries. Am J Physiol 270:H2184–H2190PubMed Wiklund L, McGregor CG, Miller VM (1996) Effects of prolonged exposure to oxygen-derived free radicals in canine pulmonary arteries. Am J Physiol 270:H2184–H2190PubMed
24.
go back to reference Zeitz O, Galambos P, Wagenfeld L, Wiermann A, Wlodarsch P, Praga R, Matthiessen ET, Richard G, Klemm M (2006) Glaucoma progression is associated with decreased blood flow velocities in the short posterior ciliary artery. Br J Ophthalmol 90:1245–1248PubMedCrossRef Zeitz O, Galambos P, Wagenfeld L, Wiermann A, Wlodarsch P, Praga R, Matthiessen ET, Richard G, Klemm M (2006) Glaucoma progression is associated with decreased blood flow velocities in the short posterior ciliary artery. Br J Ophthalmol 90:1245–1248PubMedCrossRef
25.
go back to reference Zeitz O, Maass AE, Van Nguyen P, Hensmann G, Kogler H, Moller K, Hasenfuss G, Janssen PM (2002) Hydroxyl radical-induced acute diastolic dysfunction is due to calcium overload via reverse-mode Na(+)-Ca(2+) exchange. Circ Res 90:988–995PubMedCrossRef Zeitz O, Maass AE, Van Nguyen P, Hensmann G, Kogler H, Moller K, Hasenfuss G, Janssen PM (2002) Hydroxyl radical-induced acute diastolic dysfunction is due to calcium overload via reverse-mode Na(+)-Ca(2+) exchange. Circ Res 90:988–995PubMedCrossRef
26.
go back to reference Zeitz O, Schlichting L, Richard G, Strauss O (2006) Lack of antioxidative properties of vitamin C and pyruvate in cultured retinal pigment epithelial cells. Graefes Arch Clin Exp Ophthalmol Zeitz O, Schlichting L, Richard G, Strauss O (2006) Lack of antioxidative properties of vitamin C and pyruvate in cultured retinal pigment epithelial cells. Graefes Arch Clin Exp Ophthalmol
27.
go back to reference Zweier JL, Kuppusamy P, Williams R, Rayburn BK, Smith D, Weisfeldt ML, Flaherty JT (1989) Measurement and characterization of postischemic free radical generation in the isolated perfused heart. J Biol Chem 264:18890–18895PubMed Zweier JL, Kuppusamy P, Williams R, Rayburn BK, Smith D, Weisfeldt ML, Flaherty JT (1989) Measurement and characterization of postischemic free radical generation in the isolated perfused heart. J Biol Chem 264:18890–18895PubMed
Metadata
Title
Influence of oxygen free radicals on the tone of ciliary arteries: a model of vasospasms of ocular vasculature
Authors
Oliver Zeitz
Lars Wagenfeld
Nick Wirtz
Peter Galambos
Natalya Matthiesen
Anne Wiermann
Gisbert Richard
Maren Klemm
Publication date
01-09-2007
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 9/2007
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-006-0526-9

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