title: Neuropeptide Y is released from human mammary and radial vascular biopsies and is a functional modulator of sympathetic cotransmission.
abstract: The role of neuropeptide Y (NPY) as a modulator of the vasomotor responses mediated by sympathetic cotransmitters was examined by electrically evoking its release from the perivascular nerve terminals of second- to third-order human blood vessel biopsies and by studying the peptide-induced potentiation of the vasomotor responses evoked by exogenous adenosine 5' triphosphate (ATP) and noradrenaline (NA). Electrical depolarization of nerve terminals in mammary vessels and radial artery biopsies elicited a rise in superfusate immunoreactive NPY (ir-NPY), which was chromatographically identical to a standard of human NPY (hNPY); a second peak was identified as oxidized hNPY. The amount released corresponds to 4-6% of the total NPY content in these vessels. Tissue extracts also revealed two peaks; hNPY accounted for 68-85% of the ir-NPY, while oxidized hNPY corresponded to 7-15%. The release process depended on extracellular calcium and on the frequency and duration of the electrical stimuli; guanethidine blocked the release, confirming the peptide's sympathetic origin. Assessment of the functional activity of the oxidized product demonstrated that while it did not change basal tension, the NA-evoked contractions were potentiated to the same extent as with native hNPY. Moreover, NPY potentiated both the vasomotor action of ATP or NA alone and the vasoconstriction elicited by the simultaneous application of both cotransmitters. RT-PCR detected the mRNA coding for the NPY Y(1) receptor. In summary, the release of hNPY or its oxidized species, elicited by nerve terminal depolarization, coupled to the potentiation of the sympathetic cotransmitter vasomotor responses, highlights the modulator role of NPY in both arteries and veins, strongly suggesting its involvement in human vascular sympathetic reflexes.
authors.affiliation: Instituto Milenio para Biología Fundamental y Aplicada, Departamento de Fisiología, Facultad de Ciencias Biológicas, Santiago, Chile.
authors.forename: M V
authors.initials: MV
authors.lastname: Donoso
authors.forename: R
authors.initials: R
authors.lastname: Miranda
authors.forename: M J
authors.initials: MJ
authors.lastname: Irarrázaval
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Huidobro-Toro
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000378:metabolism*; D000368:Aged; D001706:Biopsy; D002118:Calcium / Q000378:metabolism; D004357:Drug Synergism; D004558:Electric Stimulation; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000294:innervation* / Q000473:pathology / Q000502:physiology*; D008875:Middle Aged; D009478:Neuropeptide Y / Q000378:metabolism* / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D017534:Radial Artery / Q000294:innervation* / Q000473:pathology / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D013565:Sympatholytics; D013566:Sympathomimetics; C097212:neuropeptide Y-Y1 receptor; D000255:Adenosine Triphosphate; D002118:Calcium; D009638:Norepinephrine; D006145:Guanethidine