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Rationale  Nebivolol is known to have beta-1 blocker activity, but it was also suggested that it elicits relaxation of the peripheral arteries in part via release of nitric oxide (NO). However, the effect of nebivolol on the vasomotor tone of cerebral arteries is still unclear.    Objective  To assess the effects of nebivolol on the diameter of isolated rat basilar arteries (BA) in control, in the presence of inhibitors of vasomotor signaling pathways of know action and hemolysed blood.    Methods and Results  Vasomotor responses were measured by videomicroscopy and the intracellular Ca 2+  by the Fura-2 AM ratiometric method. Under control conditions, nebivolol elicited a substantial dilation of the BA (from 216±22 to 394±20 μm; p<0.05) in a concentration-dependent manner (10 −7  to 10 −4  M). The dilatation was significantly reduced by endothelium denudation or by L-NAME (inhibitor of NO synthase) or by SQ22536 (adenylyl cyclase blocker). Dilatation of BA was also affected by beta-2 receptor blockade with butoxamine, but not by the guanylate cyclase blocker ODQ. Interestingly, beta-1 blockade by atenolol inhibited nebivolol-induced dilation. Also, the BK Ca  channel blocker iberiotoxin and K Ca  channel inhibitor TEA significantly reduced nebivolol-induced dilation. Nebivolol significantly reduced smooth muscle Ca 2+  level, which correlated with the increases in diameters and moreover it reversed the hemolysed blood-induced constriction of BA.    Conclusions  Nebivolol seems to have an important dilator effect in cerebral arteries, which is mediated via several vasomotor mechanisms, converging on the reduction of smooth muscle Ca 2+  levels. As such, nebivolol may be effective to improve cerebral circulation in various diseased conditions, such as hemorrhage.

The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i