Therapeutic dose of nebivolol, a nitric oxide-releasing β-blocker, reduces atherosclerosis in cholesterol-fed rabbits

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• 作者：Filomena de Nigris ; Francesco Paolo Mancini ; Maria Luisa Balestrieri ; Russell Byrns ; Carmela Fiorito ; Sharon Williams-Ignarro ; Antonio Palagiano ; Ettore Crimi ; Louis J. Ignarro ; Claudio Napoli
• 关键词：Nitric oxide ; Carvedilol ; Nebivolol ; Atherosclerosis ; Rabbit
• 刊名：Nitric Oxide
• 出版年：2008
• 出版时间：August 2008
• 年：2008
• 卷：19
• 期：1
• 页码：57-63
• 全文大小：563 K

文摘

Nitric oxide (NO) exerts a plethora of vascular beneficial effects. The NO-releasing β-blocker nebivolol is a racemic mixture of d/l-enantiomers that displays negative inotropic as well as direct vasodilating activity. The in vivo antiatherogenic activity of therapeutic doses of the β-blocker with antioxidant properties carvedilol (12.5 mg/day) or nebivolol (5 mg/day) was tested in cholesterol-fed rabbits. Animals received a 1 % cholesterol-rich diet alone (controls) or mixed with drugs (treated animals) for 8 weeks. While it did not affect hyperlipidemia, nebivolol inhibited the development of atherosclerosis, expressed as computer-assisted imaging analysis of aortic area covered by lesions (23.3 ± 4.1 % in treated vs 38.2 ± 6.4 % in control animals, p < 0.01). Differently, in our experimental condition of therapeutic drug doses, this antiatherogenic effect did not reach statistical significance in rabbits treated with carvedilol (32.5 ± 5.1 % aortic area covered by lesions, p = NS vs controls). Plasma nitrates increased in rabbits treated with nebivolol while both β-blockers reduced LDL oxidation. Moreover, nebivolol induced a consistent increase of endothelial reactivity and aortic eNOS expression compared with control animals (p < 0.05) and those receiving carvedilol (p < 0.05). Since NO may exert beneficial effects in atherosclerosis, a NO-dependent mechanism could explain this data. These observations suggest that the NO-releasing β-blocker, nebivolol, might represent an effective pharmacological approach for preventing atherosclerotic lesion progression.