title: Cardiovascular effects and cardiopulmonary plasma gradients following intravenous infusion of neuropeptide Y in humans: negative dromotropic effect on atrioventricular node conduction.
abstract: Neuropeptide Y (NPY) is co-released with noradrenaline from sympathetic nerves, has a strong vasoconstrictive action, and causes an attenuation of parasympathetic action in animal experiments. The plasma level of NPY is greatly elevated in patients with congestive heart failure, but the clinical relevance of this finding is unclear. Central haemodynamic effects, cardiac conduction system electrophysiology and coronary sinus blood flow were therefore studied in two sets of experiments, each carried out on seven healthy men. In the first series, NPY was given intravenously at doses of 3, 10 and 30 pmol.min(-1).kg(-1), and in the second it was given as a bolus injection of 90, 200 or 900 pmol/kg, which resulted in plasma concentrations similar to those seen in heart failure patients. During continuous infusion of NPY, systemic blood pressure increased slightly, but myocardial perfusion, cardiac output, pulmonary arterial pressure, cardiac conduction intervals and atrioventricular (AV) node functional measures remained unchanged. In contrast, the bolus injection of NPY evoked prolongation and block (in four out of seven subjects) of AV node conduction, but did not affect haemodynamic variables, apart from a minor increase in systemic blood pressure. Impaired AV node conduction is a novel observation, which might reflect a baroreceptor-mediated vagal reflex, or - more likely - an NPY-induced direct negative dromotropic effect, caused by a reduction of the L-type calcium current as observed in vitro, or a combination of the two.
authors.affiliation: Department of Cardiology, Söder Hospital, SE-118 83 Stockholm, Sweden. bengt.ullman@sos.sll.se
authors.forename: Bengt
authors.initials: B
authors.lastname: Ullman
authors.forename: John
authors.initials: J
authors.lastname: Pernow
authors.forename: Jan M
authors.initials: JM
authors.lastname: Lundberg
authors.forename: Hans
authors.initials: H
authors.lastname: Aström
authors.forename: Lennart
authors.initials: L
authors.lastname: Bergfeldt
mesh_terms: D000328:Adult; D001283:Atrioventricular Node / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D009478:Neuropeptide Y / Q000097:blood / Q000494:pharmacology* / Q000502:physiology
chemical_list: D009478:Neuropeptide Y