The effects of a novel neuropeptide Y (NPY) Y1 receptor antagoniston resting mean blood pressure (MBP) and heart rate (HR) were observed inconscious spontaneously hypertensive rats (SHR). The interference of theantagonist with cardiovascular responses to mental stress andadministration of exogenous NPY were also investigated. SHR were randomlyreceived either the NPY Y1 receptor antagonist (BIBP 3226; n = 11)or its inactive enantiomer (BIBP 3435; n = 11) as an infusion (6mg/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 significantlyattenuated by antagonist infusion (P < 0.05, respectively), and theeffect lasted at least 1 hour after the end of the infusion. Plasmacatecholamine levels in response to stress were not significantly differentbetween the two groups. The results suggest that endogenous NPY Y1-receptormechanisms may be of minor importance in short-term regulation of MBP andHR in conscious adult SHR, but may be involved in the response to mentalstress.