DIFFERENTIAL VASCULAR EFFECTS OF NEUROPEPTIDE-Y (NPY) SELECTIVE RECEPTOR AGONISTS

Neuropeptide Y (NPY) increases blood pressure either directly or indirectly by potentiating the effect of various vasoconstrictors. Only one (the Y-1-receptor) of two subtypes of receptors (Y-1 and Y-2) is thought to mediate the vascular smooth muscle contraction. To test this hypothesis we challenged isolated rat mesenteric arteries that had a functional endothelium with (1-36) NPY and with specific Y-1-receptor ([Leu(31), Pro(34)] NPY) and Y-2-receptor ([Ahx(5-24), gamma-Glu(2)-epsilon-Lys(30)] NPY) agonists. The Y-1-receptor agonist elicited a contractile response similar to that of NPY, whereas the Y-2-receptor agonist had no effect on wall tension. We also found that the presence of a functional endothelium has no influence on the contractile response to NPY. From these data we conclude that the direct contractile effect of NPY in the mesenteric artery is mediated by stimulation of Y-1-receptors and is not endothelium-dependent.