Cardiovascular effects and cardiopulmonary plasma gradients following intravenous infusion of neuropeptide Y in humans: negative dromotropic effect on atrioventricular node conduction

• Published in: Clinical science (1979) Vol. 103; no. 6; pp. 535 - 542
• Main Authors: ULLMAN, Bengt, PERNOW, John, LUNDBERG, Jan M, ASTRÖM, Hans, BERGFELDT, Lennart
• Format: Journal Article
• Language: English
• Published: London Portland Press 01.12.2002
• Subjects: Adult; Atrioventricular Node - drug effects; Atrioventricular Node - physiology; Biological and medical sciences; Blood Pressure - drug effects; Coronary Circulation - drug effects; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrocardiography - drug effects; Fundamental and applied biological sciences. Psychology; General aspects; Heart Rate - drug effects; Hemodynamics - drug effects; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Medicin och hälsovetenskap; Neural Conduction - drug effects; Neuropeptide Y - blood; Neuropeptide Y - pharmacology; Neuropeptide Y - physiology; Vertebrates: cardiovascular system; Heart; Human; Neuropeptide Y; Conduction; Intravenous administration; Healthy subject; Continuous; Peptide hormone; Electrophysiology; Male; Bolus injection; Perfusion; Atrioventricular node; Hemodynamics
• ISSN: 0143-5221; 1470-8736
• DOI: 10.1042/cs1030535

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.