title: No evidence of nitrate tolerance caused by nebivolol.
abstract: BACKGROUND
  Continuous long-term treatment with nitrates may cause nitrate tolerance. Nebivolol is a highly selective beta1-adrenergic antagonist with additional nitric oxide (NO)-mediated vasodilatory effects. However, there have been no investigations into whether or not the long-term administration of nebivolol might cause nitrate tolerance.
  
  
  METHODS
  We performed a randomized, double-blind, placebo-controlled, cross-over study in 16 healthy men. Subjects received 5 mg nebivolol or placebo once daily for 8 days in random order divided by a drug-free interval of 2 weeks. Forearm blood flow (FBF) was measured by venous occlusion plethysmography 3 h after oral intake of the first and last doses of nebivolol and placebo, respectively. FBF was measured again following the intravenous administration of 4 μg nitroglycerin/kg body weight/min for 5 min.
  
  
  RESULTS
  Following 8 days of continuous intake of placebo, nitroglycerin increased FBF by 54% (p < 0.05), whereas nitroglycerin increased FBF by 96% (p < 0.01) following 8 days of continuous intake of nebivolol, and the increase after 8 days of nebivolol was significantly (p < 0.05) more pronounced than after 8 days of placebo.
  
  
  CONCLUSIONS
  These findings indicate no evidence of nitrate tolerance caused by long-term administration of nebivolol. On the contrary, long-term intake of nebivolol increases rather than decreases the NO-mediated vasodilating effects.
authors.affiliation: Universitätsklinik für Innere Medizin, Abteilung für Kardiologie, Auenbruggerplatz 15, A-8036 Graz, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Stoschitzky
authors.forename: Gergana
authors.initials: G
authors.lastname: Stoschitzky
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.forename: Thomas
authors.initials: T
authors.lastname: Wascher
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004361:Drug Tolerance; D004983:Ethanolamines / Q000494:pharmacology*; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D000068577:Nebivolol; D005996:Nitroglycerin / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D005996:Nitroglycerin
keywords: beta-blockers; nitrate tolerance; nitrates