Cardiac function in neuropeptide Y Y4 receptor-knockout mice.
Autonomic control of cardiovascular function in neuropeptide Y (NPY) Y4 receptor-knockout mice was investigated using pancreatic polypeptide (PP), NPY and specific agonists and antagonists for other NPY receptors well characterised in cardiovascular function. Y4 receptor-knockout mice, anaesthetised with sodium pentobarbitone, displayed slower heart rate, indicated by a higher pulse interval and lower blood pressure compared to control mice. After vagus nerves were cut heart rate increased but was still significantly slower than in control mice. PP had no effect on blood pressure or cardiac vagal activity in either group of mice, which was consistent with earlier studies in other species. Injection of NPY evoked an increase in blood pressure but the response was significantly reduced in Y4 receptor-knockout mice compared to the controls. The reduction in pressor activity was not Y1 mediated as the selective Y1 antagonist, BIBP 3226, was effective in blocking NPY pressor activity in knockout mice. In addition, cardiac vagal inhibitory activity evoked by low doses of NPY was also reduced when compared to control responses. As N-acetyl [Leu(28, 31)] NPY 24-36 inhibited vagal activity dose dependently in both groups of mice with no difference in response at any dose, it is unlikely that this effect also is receptor mediated. We propose that the reduced vasoconstrictor and vagal inhibitory activity evoked by NPY in Y4 receptor-knockout mice is due to a lack of adrenergic tone bought about by a proposed reduction in sympathetic activity, possibly resulting from altered NPY activity secondarily affecting adrenergic transmission. We conclude that Y4 receptor deletion disrupts autonomic balance within the cardiovascular system.
Smith-White
Margaret A
MA
Prince of Wales Medical Research Institute, University of New South Wales, Barker St., Randwick, 2031 Sydney, Australia. m.smith-white@unsw.edu.au
Herzog
Herbert
H
Potter
Erica K
EK
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology; D010191:Pancreatic Polypeptide / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology / Q000601:surgery
C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C109491:neuropeptide Y4 receptor; D010191:Pancreatic Polypeptide; D001120:Arginine