Effects of Racemic Nebivolol and Its Stereoisomers on Rat Aortic Segments in Two Age Groups

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.