Downregulation of beta-adrenergic receptor-mediated function during sodium restriction in humans

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.