Nitric oxide mediated venodilator effects of nebivolol (1994)

Author(s): A. J. Bowman;C. P. Chen;G. A. Ford

  • : Nitric oxide mediated venodilator effects of nebivolol

Abstract: 1. Nebivolol, a selective beta 1-adrenoceptor antagonist with antihypertensive effects, has haemodynamic effects suggestive of a direct vasodilator action. 2. The dorsal hand vein technique was used to determine whether nebivolol has venodilator action in vivo in man. 3. Nebivolol and atenolol were infused into the phenylephrine preconstricted superficial hand veins of 11 healthy male volunteers. In separate studies L-NMMA (0.1 microgram min-1) was pre- and co-infused with nebivolol to determine whether nitric oxide (NO) mediated mechanisms were present. Further studies with prostaglandin F2 alpha (PGF2 alpha) preconstriction were performed to exclude an alpha-adrenergic antagonistic effect of nebivolol. Effects of L-NMMA infusion on nitroglycerin venodilation were also determined. 4. Nebivolol produced a dose dependent venodilation, (72 +/- 18% maximum), whereas atenolol produced no significant venodilation. At doses of nebivolol producing plasma concentrations comparable with plasma levels achieved after standard oral dosing (10(-13)-10(-12) mol min-1) small (14 +/- 6% and 23 +/- 8%) but significant (P < 0.05) venodilation was observed. 5. The venodilator response to nebivolol was significantly reduced by infusion of L-NMMA (maximum dilation 18% vs 72%, P < 0.01). Venodilator responses to nitroglycerin were unaffected by L-NMMA infusion. A venodilator effect to nebivolol was also seen following preconstriction with PgF2 alpha (40 +/- 20% maximum). 6. Nebivolol has nitric oxide mediated, venodilator effects in man.

Notes: 0306-5251 Clinical Trial Controlled Clinical Trial Journal Article

  • Short Title: Nitric oxide mediated venodilator effects of nebivolol
  • Date: Sep
  • Journal: Br J Clin Pharmacol
  • Volume: 38
  • Issue: 3
  • Pages: 199-204
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Adrenergic beta-Antagonists/administration & dosage/*pharmacology Adult Antihypertensive Agents/administration & dosage/*pharmacology Arginine/administration & dosage/analogs & derivatives/pharmacology Atenolol/administration & dosage/pharmacology Benzopyrans/administration & dosage/*pharmacology Comparative Study Dinoprost/administration & dosage/pharmacology Dose-Response Relationship, Drug Drug Interactions Drug Therapy, Combination Ethanolamines/administration & dosage/*pharmacology Hand/blood supply Human Infusions, Intravenous Male Nitric Oxide/antagonists & inhibitors/*metabolism Nitroglycerin/administration & dosage/pharmacology Vasodilation/*drug effects Vasodilator Agents/administration & dosage/*pharmacology Veins/drug effects/metabolism omega-N-Methylarginine


Professor Gary Ford
Strategic Research Advisor