NITRIC-OXIDE MEDIATED VENODILATOR EFFECTS OF NEBIVOLOL

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 mu g min(-1)) was pre- and co-infused with nebivolol to determine whether nitric oxide (NO) mediated mechanisms were present. Further studies with prostaglandin F-2 alpha (PGF(2 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 PgF(2 alpha), (40 +/- 20% maximum). 6 Nebivolol has nitric oxide mediated, venodilator effects in man.