Novel Neuropeptide Y Receptor Antagonists Block Vasoconstriction in the Hamster Cheek Pouch Microcirculation

• Published in: Microvascular research 1997-03, Vol.53 (2), p.167-172
• Main Authors: Kim, Daekyung, Durán, Walter T.R., Daniels, Alejandro J., Durán, Walter N.
• Format: Article
• Language: English
• Subjects: Animals; Arterioles - drug effects; Biological and medical sciences; Blood Pressure - drug effects; Blood vessels and receptors; Capillary Permeability - drug effects; Cheek - blood supply; Cricetinae; Fundamental and applied biological sciences. Psychology; Hematocrit; Male; Mesocricetus; Microcirculation - drug effects; Oligopeptides - pharmacology; Receptors, Neuropeptide Y - antagonists & inhibitors; Vasodilator Agents - pharmacology; Vertebrates: cardiovascular system
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1006/mvre.1996.1991

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-assisted image analysis. Changes in arteriolar diameter served as an index of vasomotor alterations. Fluorescein isothiocyanate-labeled Dextran 150 served as a tracer for measurements of macromolecular transport. GW 383 and GW 1229, two novel NPY receptor antagonists, were applied topically in separate experiments. Pretreatment with 10−5, 10−6and 10−7MGW 383 and with 10−6and 10−8MGW 1229 attenuated the vasoconstriction induced by 10−7MNPY in a dose-dependent manner. Furthermore, pretreatment with 10−7and 10−8MGW 1229 significantly inhibited the 10−9MNPY-induced vasoconstriction. At these doses, the NPY antagonists did not alter microvascular permeability. Our results demonstrate that the novel NPY antagonists inhibit the vasoconstriction induced by NPY in the hamster cheek pouch microcirculation. We suggest that the inhibition is due to binding of antagonists to Y1-type NPY receptors.