Effects of Racemic Nebivolol and Its Stereoisomers on Rat Aortic Segments in Two Age Groups
Ulya Keskin
Department of Pharmacology, Faculty of Medicine, Baskent University, Turkey.
Oguzhan Ekin Efe *
Department of Pharmacology, Faculty of Medicine, Baskent University, Turkey.
Meral Tuncer
Department of Pharmacology, Faculty of Medicine, Baskent University, Turkey.
*Author to whom correspondence should be addressed.
Abstract
Objectives: We aimed to investigate the effects of racemic, D- and L-nebivolol in aortic segments obtained from rats of two ages to determine whether age- or stereoisomer-related differences occurred in the relaxation of aortic segments contracted with phenylephrine.
Background: Nebivolol, an antihypertensive drug with reported beta adrenergic receptor blocking effects, is clinically administered as a racemic mixture with D and L isomers. The D isomer of nebivolol is more selective than the L isomer for blocking beta-1 adrenergic receptors, whereas L-nebivolol produces greater nitric oxide (NO)-mediated vasodilation.
Methods: Aortic segments were isolated from male Wistar rats aged 4 and 8 months. Relaxations were obtained with three forms of nebivolol. The protocol was repeated following preincubation with NG-nitro-L-arginine methyl ester (L-NAME) alone or with indomethacin.
Results: A significant age-related difference in relaxation was found only for racemic nebivolol and only at a concentration of 10−4 M. L-NAME and indomethacin did not affect the relaxations. Nebivolol noncompetitively shifted the phenylephrine concentration-response curve.
Conclusion: Relaxation by nebivolol was not dependent on age or stereoisomer. Neither cyclooxygenase metabolites nor NO played a role in relaxations. Results suggest that inhibition of phenylephrine contractions by nebivolol is due to blockade of alpha adrenergic receptor activity.
Keywords: Nebivolol and stereoisomers, nitric oxide (NO), L-NAME, indomethacin, phenylephrine