Microcirculatory Dynamics of Neuropeptide Y

Abstract

We used the hamster cheek pouch microcirculation to investigate by intravital microscopy the effects of neuropeptide Y (NPY) on arteriolar diameter, leukocyte adhesion to microvascular endothelium, and postcapillary venular permeability. We applied NPY topically for 3 min at concentration of 10-7, 10-9, and 10-11M. We quantified arteriolar diameter and permeability changes by digital image analysis. We used the mass of fluorescein isothiocyanate-Dextran 150 accumulated around postcapillary venules (10-30 μm) to calculate extravasation rates of macromolecules. We also measured the number of adhering white cells per 100-μm length of postcapillary venules using acridine orange to label white blood cells. At the applied doses, NPY did not alter either microvascular permeability to macromolecules or leukocyte adhesion to microvascular walls. NPY, in a dose-dependent manner, constricted arterioles ranging in control diameter from 10 to 60 μm. Vasoconstriction was strongest in arterioles ranging in diameter from 30 to 39 μm at a concentration of NPY of 10-7M. The Y1-type NPY receptor agonist, Leu31, Pro34-NPY, was as potent as NPY, whereas the carboxy-terminal fragment NPY 13-36 had no activity, indicating that the hamster cheek pouch microvasculature expresses the Y1 type of NPY receptor. We also blocked α-adrenergic receptors to test whether norepinephrine is required for NPY-induced vasoconstriction. This blockade did not inhibit the vasoconstriction caused by exogenous NPY. Our results demonstrate that (1) NPY modulates microvascular hemodynamics by changes in arteriolar diameter, (2) the NPY receptor on the hamster cheek pouch microvasculature is of the Y1 type, and (3) exogenous NPY-induced vasoconstriction is independent of the activity of endogenous norepinephrine.