Ageing is known to affect the reactivity of brain vasculature and its ability to regulate cerebral blood flow. Here, we tested whether ageing affects the cross-talk between NO and cAMP/Epac signaling in isolated basilar arteries from 11-12 week and 16-24 month old mice. In isometrically mounted arteries from young mice inhibition of e- and nNOS with 100 µM L-NAME and specific inhibition of nNOS by 1 µM L-NPA increased basal tone by respectively 9 % and 11 % of maximal activation (F_max) elicited by U46619 (3 µM) + L-NAME or L-NPA. In contrast, in arteries from old mice, L-NAME increased basal tone by 23 % (n = 4) and L-NPA by only 12 % (n = 3) of F_max. In young mice the pEC₅₀ value of U46619 was shifted from 6.6 (control) to 7.1 by L-NAME (n=6) and by L-NPA (n=3). In aged arteries both inhibitors increased pEC₅₀ value from 7.0 (control) to 7.3 (n=3-4). The Epac activator 8-pCPT-O´-Me-cAMP (100 and 300 µM) relaxed submaximally preconstricted (0.3 µM U46619) arteries. Relaxation was attenuated by L-NAME in aged but not in young arteries. In conclusion, our results suggest that (i) in aged arteries NOS activity is required for EPAC-induced dilation, (ii) nNOS attenuates U46419 induced contraction in young and to a lesser extend in old arteries, and (iii) regulation of basal tone in young mice is predominantly nNOS-dependent whereas in aged arteries it involves both n- and eNOS.