title: Nitric-oxide-mediated relaxations in salt-induced hypertension: effect of chronic beta1 -selective receptor blockade.
abstract: BACKGROUND
  Nebivolol is a new beta1-selective adrenergic receptor antagonist with a direct vasorelaxant effect that involves activation of the l-arginine-nitric oxide (NO) pathway. Therefore, treatment with nebivolol may protect against endothelial injury in hypertension.
  
  
  OBJECTIVE
  To investigate whether chronic selective beta1-blockade with nebivolol could prevent endothelial dysfunction in salt-induced hypertension, and to compare it with atenolol.
  
  
  METHODS
  Dahl salt-sensitive rats were treated for 8 weeks with standard chow or chow containing 4% NaCl alone or in combination with nebivolol (10 mg/kg per day) or atenolol (100 mg/kg per day). Isometric tension was continuously recorded in isolated aorta and small mesenteric arteries. Constitutive NO synthase (cNOS) activity was determined by [3H]citrulline assay.
  
  
  RESULTS
  Chronic salt administration increased systolic blood pressure by 38 +/- 5 mmHg in salt-treated rats as compared with that in control rats. Both nebivolol and atenolol prevented a salt-induced increase in pressure. cNOS activity was significantly decreased by a high-salt diet. The impairment of endothelium-dependent relaxations in response to acetylcholine in salt-treated rats was prevented only by nebivolol, in both large and small arteries. In contrast, the reduced endothelium-independent relaxations and contractions in response to sodium nitroprusside and endothelin-1, respectively, were restored by both drugs. Nebivolol, but not atenolol, restored cNOS activity.
  
  
  CONCLUSIONS
  Despite nebivolol and atenolol having the same blood-pressure-decreasing effect, only nebivolol was able to prevent endothelial dysfunction. This study demonstrates for the first time that the acute NO-mediated vasodilatory action of nebivolol is also present during chronic treatment. Hence, nebivolol might become a new therapeutic tool with which to exert vascular protective effects against end-organ damage in conditions associated with NO deficiency.
authors.affiliation: Department of Cardiology and Cardiovascular Research, University Hospital, Zürich, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cosentino
authors.forename: Sandro
authors.initials: S
authors.lastname: Bonetti
authors.forename: Rudolf
authors.initials: R
authors.lastname: Rehorik
authors.forename: Masato
authors.initials: M
authors.lastname: Eto
authors.forename: Gabriele
authors.initials: G
authors.lastname: Werner-Felmayer
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001262:Atenolol / Q000494:pharmacology; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D000068577:Nebivolol; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D020303:Rats, Inbred Dahl; D012965:Sodium Chloride; D013599:Systole; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D014665:Vasodilator Agents; D000068577:Nebivolol; D009569:Nitric Oxide; D012965:Sodium Chloride; D001262:Atenolol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat