MICROCIRCULATORY DYNAMICS OF NEUROPEPTIDE-Y

We used the hamster cheek pouch microcirculation to investigate by int ravital microscopy the effects of neuropeptide Y (NPY) on arteriolar d iameter, leukocyte adhesion to microvascular endothelium, and postcapi llary venular permeability. We applied NPY topically for 3 min at conc entrations of 10(-7), 10(-9), and 10(-11) M. We quantified arteriolar diameter and permeability changes by digital image analysis. We used t he mass of fluorescein isothiocyanate-Dextran 150 accumulated around p ostcapillary venules (10-30 mu m) to calculate extravasation rates of macromolecules. We also measured the number of adhering white cells pe r 100-mu m length of postcapillary venules using acridine orange to la bel white blood cells. At the applied doses, NPY did not alter either microvascular permeability to macromolecules os leukocyte adhesion to microvascular walls. NPY, in a dose-dependent manner, constricted arte rioles ranging in control diameter from 10 to 60 mu m. Vasoconstrictio n was strongest in arterioles ranging in diameter from 30 to 39 mu m a t a concentration of NPY of 10(-7) M. The Y1-type NPY receptor agonist , Leu(31), Pro(34)-NPY, was as potent as NPY, whereas the carboxy-term inal fragment NPY 13-36 had no activity, indicating that the hamster c heek pouch microvasculature expresses the Y1 type of NPY receptor. We also blocked cr-adrenergic receptors to test whether norepinephrine is required for NPY-induced vasoconstriction. This blockade did not inhi bit the vasoconstriction caused by exogenous NPY. Our results demonstr ate that (1) NPY modulates microvascular hemodynamics by changes in ar teriolar diameter, (2) the NPY receptor on the hamster cheek pouch mic rovasculature is of the Y1 type, and (3) exogenous NPY-induced vasocon striction is independent of the activity of endogenous norepinephrine. (C) 1994 Academic Press, Inc.