Using the selective neuropeptide Y Y1 receptor antagonist, BIBP3226 [(N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-argininamide], the role of endogenous neuropeptide Y in mediating vasoconstrictor responses to adrenergic nerve stimulation was investigated by recording isometric force from isolated rat tail artery segments. BIBP3226 had no effect on contractile responses to adrenergic nerve stimulation (10 pulses; 0.5-2 Hz), but it completely blocked the enhancement of contraction produced by exogenous neuropeptide Y. When frequency and train length of the transmural nerve stimulation were increased (100 pulses; 1-16 Hz), contractile responses were still unaffected by BIBP3226. A peptidase inhibitor mixture known to increase responses to exogenous neuropeptide Y was added; however, BIBP3226 still did not influence contractile responses to adrenergic nerve stimulation. Thus, contractile responses to adrenergic nerve stimulation in the rat tail artery do not appear to involve the release and postjunctional action of endogenous neuropeptide Y; however, exogenous neuropeptide Y does potentiate these responses by acting on Y1 receptors.