Distinction of NPY receptors in vitro and in vivo. II. Differential effects of NPY and NPY-(18-36).
We have studied the hemodynamic effects of neuropeptide Y (NPY) and its COOH-terminal fragment NPY-(18-36) in conscious rats. Intra-arterial injection of NPY rapidly elevated systemic vascular resistance (SVR), which remained high for greater than 30 min. Cardiac output (CO) decreased, and it remained low for greater than 30 min. Accordingly, blood pressure rose only transiently and returned to base-line values within 5 min. The reduction of CO could be attributed to a decreased stroke volume with an only marginal reduction of heart rate. Thus a direct cardiodepressive effect of NPY rather than baroreflex activation appears to be the major cause of the reduced CO. In vitro experiments excluded the possibility that NPY has direct negative inotropic effects and suggest that its cardiodepressive action is caused by coronary vasoconstriction or by presynaptic inhibition of norepinephrine release. Intra-arterial injections of NPY-(18-36) caused different hemodynamic effects. NPY-(18-36) decreased CO in a manner similar to that seen with NPY but initially did not elevate SVR, resulting overall in a reduced blood pressure. Only later, when blood pressure was reduced, was an elevation of SVR observed, which could be associated with increased plasma levels of catecholamines, angiotensin II, vasopressin, and NPY. Thus NPY-(18-36) mimics the cardiac effects of NPY but does not elicit its vascular effects. As NPY-(18-36) discriminates between NPY receptor subtypes in vitro, we conclude that the cardiac and vascular effects of NPY are mediated by distinct receptor subtypes.
Scott
N A
NA
Department of Medicine, University of California, San Diego Medical Center 92103.
Michel
M C
MC
Boublik
J H
JH
Rivier
J E
JE
Motomura
S
S
Crum
R L
RL
Landon
M
M
Brown
M R
MR
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; D001127:Arginine Vasopressin; C059889:neuropeptide Y (18-36); D009638:Norepinephrine; D004837:Epinephrine