To investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor, peridopril, and the beta-adrenergic blocker, metoprolol, on plasma neuropeptide Y (NPY), and NPY receptors in aortic vascular smooth muscle cells (VSMCs) from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), both strains of rats were fed with different doses of the drugs (peridopril or metoprolol) for 7 days to get the optimal dosages. After that, 18 male SHR and 18 male age-matched WKY rats were divided into three groups: control, peridopril (2mg/kg/day) and metoprolol (2mg/kg/day). After two months of treatment, VSMCs were isolated from the media layer of the aortic wall. Results showed that the SHRs had higher plasma concentrations and binding sites/affinity for NPY as compared to WKY rats. Peridopril dose-dependently decreased plasma NPY concentrations in WKY rats, and the absolute changes of plasma NPY were greater in SHRs than in WKY rats. Metoprolol showed none of these changes. Metoprolol decreased while peridopril increased NPY binding sites/affinity in SHRs. This indicated that lowered plasma NPY concentration and decreased NPY receptor in VSMCs, might play some roles in the anti-hypertensive mechanisms mediated by ACE inhibitor and beta-adrenergic blockers.