The aim of this study was to investigate the synergism between neuropeptide Y and other vasoconstrictors (phenylephrine and serotonin) and which neuropeptide Y receptor subtype is responsible for the neuropeptide Y-induced potentiation. Exogenous neuropeptide Y (10 nM) potentiated alpha1-adrenoceptor-mediated (PE-induced) contraction in rat femoral artery permissively without its direct action, but not in the thoracic aorta. In contrast, neuropeptide Y produced no change in serotonin-induced contraction in both arteries. Increasing concentrations of neuropeptide Y caused dose-dependent potentiation of the phenylephrine-induced contraction in the femoral artery. This potentiation was blocked by a selective neuropeptide Y-Y1 receptor antagonist, BIBP3226 [(R)-N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-argininamide] (1 microM). Semiquantitative reverse transcriptase polymerase chain reaction showed the selective expression of neuropeptide Y-Y1 receptor mRNA in the femoral artery. These findings indicated that the neuropeptide Y-induced selective potentiation of alpha1-adrenoceptor-mediated contraction is mediated through neuropeptide Y-Y1 receptor in rat femoral artery.