Keywords: nebivolol, cerebral artery, vasomotor, basilar artery, isolated artery, NO, cGMP INTRODUCTION: Experimental and clinical studies have demonstrated that nebivolol has antiarrhythmic, antihypertensive effects and in peripheral arteries elicits dilation, in which mediation for nitric oxide (NO) has been suggested. However, its effect on the diameter of cerebral vessels has not been investigated. We hypothesized that nebivolol increases the diameter of isolated cerebral arteries. METHODS: Basilar arteries (BA) were isolated from male Wistar rats and were mounted into a pressure-flow myograph chamber and cannulated at both ends. Vessels were incubated until a spontaneous active diameter developed. Diameters (D) of vessels were measured with video-microscopy. Vasomotor function of vessels was studied in response to nebivolol and the nitric oxide (NO) donor sodium nitroprusside (SNP). NO synthase was inhibited by Nω-nitro-L-arginine methyl ester (L-NAME). Soluble guanylate cyclase was blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). At the end of the experiments the passive diameter of vessels (PD) was determined in Ca2+-free Krebs solution. RESULTS: The active diameter of BA was ~220 µm (n=9). Nebivolol caused significant vasodilation (10-5M: ΔD = 67±18 µm; p<0,05). Incubation of BA with L-NAME significantly reduced the active diameter (by ΔD = 25±10 µm). In the presence of L-NAME nebivolol caused significant vasodilation, similar to control conditions (10-5 M: ΔD = 47±10 µm). Also, in the presence of ODQ, nebivolol elicited significant vasodilation (10-5 M: ΔD = 87±16 µm), whereas the SNP-induced dilation was significantly decreased (SNP 10-4 M: from ΔD[1] = 126±14 µm to ΔD[2] = 1±17 µm). CONCLUSION: These findings demonstrate that in isolated cerebral arteries 1) nebivolol elicits significant dilation, 2) NO contribute to the development of basal tone, 3) but NO-cGMP pathway does not contribute significantly to the nebivolol-induced dilation. Elucidating the underlying mechanisms could contribute to a better understanding of the effects of nebivolol on cerebral circulation.