Nebivolol induces endothelium‐independent vasodilation of rat uterine arteries by a cyclic nucleotide mechanism

Aim The third generation of beta‐blockers represents a new development in the pharmacotherapy of chronic hypertension. Since hypertension develops in approximately 8% of all gestations, the aim of this study was to investigate the effect of nebivolol (NB) ‐ the most selective beta‐adrenergic receptor blocker ‐ on the uterine vasculature. Methods Resistance rat radial uterine arteries (100–150 μm) were cannulated and pressurized (50 mmHg) in an arteriograph and preconstricted 40–50% with phenylephrine prior to being exposed to NB. Intact and endothelium‐denuded arteries were used to define the vasoactive profile of NB (0.1 – 30 μM) and the underlying target cell. Preincubation with SQ22536 and ODQ was used to inhibit cGMP and cAMP signaling. Results NB produced arterial vasodilation in a concentration‐dependent manner with an EC50 value of 0.15 μM; at concentrations > 1 μM, efficacy was maximal (100%). The NB response was unaffected by endothelial removal, however, vasodilation was significantly reduced in the presence of SQ22536 or ODQ. Conclusions NB has a potent vasodilatory effect on uterine arteries that is mediated by vascular smooth muscle beta‐ARs via cAMP and cGMP signaling. The results suggest that NB may have therapeutic potential for improving uteroplacental blood flow during hypertensive pregnancy. Source of support: University of Calabria internal grant; M.I.U.R., Italy