NOVEL NEUROPEPTIDE-Y RECEPTOR ANTAGONISTS BLOCK VASOCONSTRICTION IN THE HAMSTER-CHEEK POUCH MICROCIRCULATION

We investigated the efficacy of novel neuropeptide Y (NPY) antagonists to inhibit the microcirculatory dynamics of NPY in the hamster cheek pouch microcirculation using intravital microscopy and computer-assist ed image analysis. Changes in arteriolar diameter served as an index o f vasomotor alterations. Fluorescein isothiocyanate-labeled Dextran 15 0 served as a tracer for measurements of macromolecular transport. GW 383 and GW 1229, two novel NPY receptor antagonists, were applied topi cally in separate experiments. Pretreatment with 10(-5), 10(-6) and 10 (-7) M GW 383 and with 10(-6) and 10(-8) M GW 1229 attenuated the vaso constriction induced by 10(-7) M NPY in a dose-dependent manner. Furth ermore, pretreatment with 10(-7) and 10(-8) M GW 1229 significantly in hibited the 10(-9) M NPY-induced vasoconstriction. At these doses, the NPY antagonists did not alter microvascular permeability. Our results demonstrate that the novel NPY antagonists inhibit the vasoconstricti on induced by NPY in the hamster cheek pouch microcirculation. We sugg est that the inhibition is due to binding of antagonists to Y1-type NP Y receptors. (C) 1997 Academic Press.