Objective: The third generation of b-blockers represents a new development in the pharmacotherapy of hypertension, which is a main cause of mortality worldwide. Because hypertension develops in approximately 8% of all gestations, the aim of this study was to investigate the effect of the most selective b1- adrenergic receptor (b-AR), Nebivolol (NB), on the uterine vasculature. Methods: Experiments were run on isolated, pressurized radial rat uterine arteries (f: 100- 150mm), resistance vessels that play an important role in the regulation of uterine and uteroplacental blood flow. We used intact and denuded arteries in which the endothelium was mechanically removed to define the vasoactive profile of each compound, and to probe the underlying mechanism of action. Arteries were cannulated in the chamber of an arteriograph, superfused with Hepes-PSS and changes in diameter were evaluated by a video dimension analyzer. Results: 1) NB induces vasodilation in a concentration-dependent manner; 2) Endothelial denudation does not inhibits the NB vasodilation; 3) NB acts mainly by the a-AR and partly by b-ARs 4) Vasodilation to NB was reduced in presence of cGMP or cAMP inhibitors. Conclusions: NB is a potent vasodilator of small uterine arteries. Its effects are endothelium- independent and can be explained by the activation of the adrenoreceptors and the stimulation of cGMP and cAMP in vascular smooth muscle. This is the first study to document a vasodilatory effect of NB on uterine arteries, and suggest that this form of therapy may be useful in improving uteroplacental blood flow during hypertensive pregnancy.