AJP - Endocrinology and Metabolism, Vol 257, Issue 4 E499-E504, Copyright © 1989 by American Physiological Society
Downregulation of beta-adrenergic receptor-mediated function during sodium restriction in humans
S. G. Rosen, O. A. Linares, M. J. Smith and J. B. Halter
Department of Internal Medicine, University of Michigan, Ann Arbor.
Mononuclear leukocyte (MNL) beta 2-adrenergic receptor (beta 2-AR) binding
and its linked adenylate cyclase sensitivity to isoproterenol were measured
in nine healthy humans prior to and after 7 days of dietary sodium
restriction to determine whether chronic physiological increases in plasma
norepinephrine (NE) are associated with the downregulation of
beta-AR-mediated function. Sodium restriction resulted in an increase in
the plasma NE concentration (P less than 0.02) and decreases in MNL beta
2-AR density (P less than 0.001), affinity for antagonist (P less than
0.001), and adenylate cyclase sensitivity to isoproterenol (ANOVA, P less
than 0.01). To determine whether this downregulation of MNL beta
2-AR-mediated function is related to the increased plasma NE concentration
or to increased extravascular NE release, NE kinetics was assessed using
compartmental analysis in each subject prior to and after sodium
restriction. Sodium restriction caused a decrease in the plasma NE
metabolic clearance rate (P less than 0.005) and in the volume of
distribution of NE in the intravascular compartment (P less than 0.005),
whereas the extravascular NE release rate was unchanged. Our data suggest
that the downregulation of MNL beta 2-AR-mediated function in humans during
dietary sodium restriction is a response to the increase in plasma NE.
