title: Therapeutic dose of nebivolol, a nitric oxide-releasing beta-blocker, reduces atherosclerosis in cholesterol-fed rabbits.
abstract: Nitric oxide (NO) exerts a plethora of vascular beneficial effects. The NO-releasing beta-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 beta-blocker with antioxidant properties carvedilol (12.5mg/day) or nebivolol (5mg/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 beta-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 beta-blocker, nebivolol, might represent an effective pharmacological approach for preventing atherosclerotic lesion progression.
authors.affiliation: Department of General Pathology, Excellence Research Center on Cardiovascular Diseases, Complesso S. Andrea della Dame, Via de Crecchio 7, 1st School of Medicine, II University of Naples, 80138 Naples, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: de Nigris
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Mancini
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Balestrieri
authors.forename: Russell
authors.initials: R
authors.lastname: Byrns
authors.forename: Carmela
authors.initials: C
authors.lastname: Fiorito
authors.forename: Sharon
authors.initials: S
authors.lastname: Williams-Ignarro
authors.forename: Antonio
authors.initials: A
authors.lastname: Palagiano
authors.forename: Ettore
authors.initials: E
authors.lastname: Crimi
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Ignarro
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000821:Animal Feed; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use; D000077261:Carvedilol; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000378:metabolism; D000068577:Nebivolol; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001578:Benzopyrans; D002227:Carbazoles; D002791:Cholesterol, Dietary; D004983:Ethanolamines; D008077:Lipoproteins, LDL; D011412:Propanolamines; D012333:RNA, Messenger; D000068577:Nebivolol; D000077261:Carvedilol; D009569:Nitric Oxide