Effects of Racemic Nebivolol and Its Stereoisomers on Rat Aortic Segments in Two Age Groups
Journal Title: Journal of Advances in Medicine and Medical Research - Year 2016, Vol 18, Issue 9
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.
Authors and Affiliations
Ulya Keskin, Oguzhan Ekin Efe, Meral Tuncer
Keywords
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- EP ID EP341012
- DOI 10.9734/BJMMR/2016/28626
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