Unmasking the vasoconstrictor response to neuropeptide Y and its interaction with vasodilating agents in vitro

Neuropeptide Y (NPY) is a powerful vasoconstrictor in vivo but is usually much less active on isolated blood vessels. The contractile effect of NPY was examined in the isolated rat femoral artery exposed to various degrees of vasoconstriction. The effects of NPY on the relaxation induced by vasodilator agents was also studied. NPY (< or = 1 microM) had no contractile effect. In vessels pretreated with a low concentration of phenylephrine (0.3-1.0 microM), NPY evoked a concentration-dependent contraction, which was similar in intact and in endothelium-deprived vessels. Other vessels were contracted with phenylephrine (3-10 microM) and relaxed with histamine (0.1 mM). Subsequent addition of NPY elicited a contraction which was much greater than that observed in vessels pretreated with phenylephrine only. The Y1 receptor agonist, [Pro34]NPY, but not the Y2 receptor agonist, NPY 13-36, evoked a concentration-dependent contraction in phenylephrine-pretreated vessels. Acetylcholine (ACh) induced endothelium-dependent relaxation in vessels contracted with phenylephrine. NPY (0.1 microM) induced a rightward shift of the concentration-response curve and a lower maximum relaxation in response to ACh. NPY was without effect on the dilatation evoked by nitroprusside, histamine or forskolin. In conclusion, under appropriate vasoconstrictor and vasodilator influence, NPY can act at Y1 receptors to evoke vasoconstriction in the femoral artery via endothelium-independent mechanisms. In addition, NPY seems to attenuate the endothelium-dependent relaxation induced by ACh. These actions of NPY may contribute to explain the strong vascular effects of the peptide in vivo.