NITRIC-OXIDE MEDIATED VENODILATOR EFFECTS OF NEBIVOLOL

1 Nebivolol, a selective beta(1)-adrenoceptor antagonist with antihype rtensive effects, has haemodynamic effects suggestive of a direct vaso dilator 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 superf icial 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 dete rmine whether nitric oxide (NO) mediated mechanisms were present. Furt her studies with prostaglandin F-2 alpha (PGF(2 alpha)) preconstrictio n were performed to exclude an alpha-adrenergic antagonistic effect of nebivolol. Effects of L-NMMA infusion on nitroglycerin venodilation w ere also determined. 4 Nebivolol produced a dose dependent venodilatio n, (72 +/- 18% maximum), whereas atenolol produced no significant veno dilation. At doses of nebivolol producing plasma concentrations compar able with plasma levels achieved after standard oral dosing (10(-13)-1 0(-12) mol min(-1)) small (14 +/- 6% and 23 +/- 8%) but significant (P < 0.05) venodilation was observed. 5 The venodilator response to nebi volol was significantly reduced by infusion of L-NMMA (maximum dilatio n 18% vs 72%, P < 0.01). Venodilator responses to nitroglycerin were u naffected by L-NMMA infusion. A venodilator effect to nebivolol was al so seen following preconstriction with PgF(2 alpha), (40 +/- 20% maxim um). 6 Nebivolol has nitric oxide mediated, venodilator effects in man .