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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalNitric Oxide - Biology and Chemistry
Volume19
Issue number1
DOIs
Publication statusPublished - Aug 2008

Keywords

  • Atherosclerosis
  • Carvedilol
  • Nebivolol
  • Nitric oxide
  • Rabbit

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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