Neuropeptide Y (NPY) has a wide and specific distribution in the central nervous system, and is colocalized with catecholamines in specific neuronal systems. In this study, in order to investigate the regulatory mechanisms of NPY and presynaptic α2-adrenergic receptors on central noradrenergic transmission in hypertension, we have examined the effects of NPY and the α2-agonist, UK 14, 304, on (3H)-noradrenaline (NA) release from hypothalamic slices of spontaneously hypertensive rats (SHR). Electrical stimulation (1 Hz)-evoked (3H)-NA release was significantly greater in the hypothalamic slices of SHR than in those of Wistar Kyoto rats (WKY). NPY and the α2-agonist, UK 14, 304, inhibited the stimulation-evoked (3H)-NA release in a dose-related manner. The inhibitory effects of NPY and UK 14, 304 on NA release were significantly attenuated in SHR compared with WKY. These results suggest that NPY and α2-adrenoceptors might be involved in the regulation of central sympathetic nervous activity in hypertension.