The effects of a novel neuropeptide Y (NPY) Y1 receptor antagonist on resting mean blood pressure (MBP) and heart rate (HR) were observed in conscious spontaneously hypertensive rats (SHR). The interference of the antagonist with cardiovascular responses to mental stress and administration of exogenous NPY were also investigated. SHR were randomly received either the NPY Y1 receptor antagonist (BIBP 3226; n = 11) or its inactive enantiomer (BIBP 3435; n = 11) as an infusion (6 mg/kg/h for 1.5 hours). Before, during, and after the infusion, rats were first stressed with a jet of air and then given a bolus injection of exogenous NPY (2 nmol/kg). There was no statistically significant difference of resting MBP and HR between the antagonist and enantiomer groups before, during, or after infusion. The stress-induced maximum increase in HR was significantly reduced during antagonist infusion (P < 0.05). The effects of exogenous NPY on both MBP and HR were significantly attenuated by antagonist infusion (P < 0.05, respectively), and the effect lasted at least 1 hour after the end of the infusion. Plasma catecholamine levels in response to stress were not significantly different between the two groups. The results suggest that endogenous NPY Y1-receptor mechanisms may be of minor importance in short-term regulation of MBP and HR in conscious adult SHR, but may be involved in the response to mental stress.