Purchase this article with an account.
L. Wagenfeld, O. Zeitz, O. Himpel, P. Galambos, A. Wiermann, N. Matthiesen, G. Richard, M. Klemm; Oxygen Free Radical Induced Vasospasm of Porcine Ciliary Arteries: Protective Effects of Nebivolol. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2255.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Vasospasms are discussed to play a role in the pathogenesis of glaucoma. A possible mechanism how vasospasm can be induced is a free radical exposure. For Nebivolol scavenger properties have been postulated. There are indications that Nebivolol improves ocular hemodynamics (ARVO meeting 2006, Poster-Nr.: 485-B239). Aim of this study is to investigate if a radical induced vasospasm of porcine ciliary arteries can be reduced by Nebivolol in an in vitro experiment.
Rings of isolated porcine ciliary arteries were mounted in a force myograph and kept in an almost physiological environment (Krebs-Henseleit-Buffer, pH=7.4, 37° C). Two full contractions were performed by depolarizing the arteries by rising the extracellular potassium to a concentration of 120 mM. Afterwards half maximal contractions were induced by 30mM potassium in the extracellular solution. These pre-contracted arteries were exposed to various concentrations (10-6 to 10-3 M) of Nebivolol or equivalent amounts of its solvent DMSO. Oxygen free radicals (OFR) from the Fenton reaction (H2O2 + Fe3+ -> -OH) were added to initiate the contractions. The rise in force was recorded and compared between the tested concentrations of Nebivolol. To make results more comparable all forces were normalized on the second full contraction. All statistical analysis was done with these normalized values to minimize errors.
Higher concentrations of Nebivolol lead to a more pronounced inhibition of the OFR induced vasospasm (0.22 ± 0.04 with 10-6 M Nebivolol vs. 0.27± 0.09 with equivalent amounts of DMSO, p=0.59, n=6; 0.14 ± 0.01 with 10-5 M Nebivolol vs. 0.36 ± 0.05 with DMSO, p=8*10-5, n=11; 0.09 ± 0.02 with 10-4 M Nebivolol vs. 0.38 ± 0.05 with DMSO, p=4*10-6, n=11; 0.04 ± 0.02 with 10-3 Nebivolol vs. 0.15 ± 0.03 with DMSO, p=0.01, n=6). ANOVA testing shows that this effect is dose dependent and all steps are significant except the step from 0 M to 10-6 M.
These data implicate that Nebivolol has a pronounced scavenger effect. Following our data Nebivolol has the capability to reduce OFR induced vasospasms in vitro and may have protective effects for glaucoma patients.
This PDF is available to Subscribers Only