AJP - Heart and Circulatory Physiology, Vol 259, Issue 1 174-H180, Copyright © 1990 by American Physiological Society
Distinction of NPY receptors in vitro and in vivo. II. Differential effects of NPY and NPY-(18-36)
N. A. Scott, M. C. Michel, J. H. Boublik, J. E. Rivier, S. Motomura, R. L. Crum, M. Landon and M. R. Brown
Department of Medicine, University of California, San Diego Medical Center 92103.
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.
