Beta-blockade with nebivolol enhances the acetylcholine-induced cutaneous vasodilation

Nebivolol is a selective beta(1)-adrenoceptor blocker that has a vasorelaxant activity thought to be the result of a facilitation of the release of nitric oxide from the endothelium. This study was undertaken in 12 healthy male volunteers to assess whether this compound increases the vasodilatory response to acetylcholine when administered orally at a dose commonly recommended for the treatment of cardiovascular diseases. The subjects were randomly allocated to an 8-day treatment with nebivolol (5 mg once a day) and atenolol (50 mg once a day) according to a cross-over design. The two treatments were separated by a 1-week washout period. On the first and the last day of each treatment phase, both before drug administration and 3 hours after drug administration, the forearm skin blood flow response to acetylcholine applied by iontophoresis was determined with the use of a laser Doppler scanner imaging system. The reactivity to acetylcholine was significantly increased 3 hours after the administration of nebivolol on both the first and the last day of treatment, whereas atenolol had no effect on this parameter. These data therefore indicate that nebivolol, but not atenolol, enhances the vasorelaxant activity of acetylcholine in the skin vascular bed; this is compatible with a facilitation by this beta-blocker of the endothelium-dependent vasodilation.