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

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 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 p