Protective effects of nebivolol on oxygen free radical-induced vasoconstrictions in vitro.
BACKGROUND
Disturbed ocular hemodynamics and vasospasms might be involved in the pathogenesis of glaucoma. On a clinical level there are indications for an optimization of ocular perfusion parameters in hypertensive glaucoma patients by switching a beta-adrenoceptor-antagonist therapy to nebivolol. Aim of the present study is to investigate vasoactive properties of nebivolol on ocular vasculature in vitro. Besides vasorelaxing effects, the impact of nebivolol on oxygen free radical-induced vasoconstrictions is studied.


METHODS
The experiments were carried out with ring preparations from porcine ciliary arteries. The preparations were placed in a myograph system and were kept under physiological conditions (pH 7.4, 37 degrees C, Krebs-Henseleit-Buffer, 1.75 mM Ca2+) and were stimulated by K+ depolarizations. The experiments were performed at a Nernst potential of -41 mV, which reflects half-maximal activation. For radical exposure, the preparations were superfused for 20 s in a specifically designed set-up with hydroxyl radicals generated by the Fenton reaction from H2O2 and Fe3+. NO synthase activity was modulated by adding L-arginine to the buffer.


RESULTS
At a concentration of 10-5 M nebivolol leads to a reduction of vascular tone by -8.5+/-3.4% (n=11; P=0.016) vs. +2.6+/-1.9% (n=11; n.s.) in presence of its solvent DMSO. Nebivolol (10-5 M) reduces hydroxyl radical-induced vasoconstrictions by 53+/-10% (n=11; P<0.001). Stimulation of the NO synthase by L-arginine saturation potentiates this effect.


CONCLUSIONS
Nebivolol combines vasorelaxing properties with protection against oxidative stress-induced vasoconstrictions. Both effects may be attributed to NO-releasing properties of nebivolol independently of its beta-adrenoceptor-blocking effect.
Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany.
Lars
L
Wagenfeld
Okko
O
Himpel
Peter
P
Galambos
Nataliya
N
Matthiesen
Anne
A
Wiermann
Gisbert
G
Richard
Maren
M
Klemm
Oliver
O
Zeitz
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019842:Ciliary Arteries / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D005609:Free Radicals / Q000633:toxicity*; D066298:In Vitro Techniques; D000068577:Nebivolol; D010100:Oxygen / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D001578:Benzopyrans; D004983:Ethanolamines; D005609:Free Radicals; D020011:Protective Agents; D000068577:Nebivolol; D010100:Oxygen