Plasma norepinephrine in humans: limitations in assessment of whole body norepinephrine kinetics and plasma clearance

Abstract

To investigate catecholamine residence in plasma, constant intravenous infusions of increasing duration (20, 40, and 80 min) of [3H]norepinephrine [( 3H]NE), [3H]isoproterenol [( 3H]IP) IP) and a reference substance: 131I-labeled hippurate were performed in six normal volunteers. In contrast to [3H]IP and 131I-hippurate, whole body clearance from plasma of [3H]NE, as obtained from infusion rate divided by plasma concentration of tracer [1.74 +/- 0.64 (SD) 1/min] was significantly higher than the value obtained by total tracer infusion divided by total plasma area of tracer (1.27 +/- 0.51, P less than 0.01). Mean residence time in plasma (theta) after stopping the infusion of [3H]NE increased along an almost straight line with progressive infusion time, theta of 131I-hippurate increased less, and constant values were recorded after 40 min infusion of [3H]IP. Our results suggest the presence of a very large (cellular) pool from which a reversible transport of [3H]NE back into plasma takes place. The plasma clearance of tracer NE, as determined from infusion rate and plasma concentration of tracer, includes transport to and accumulation in this large store. Thus the "final metabolic clearance," reflecting irreversible removal of NE, is smaller than previously estimated due to recycling through the plasma space. Attention has been drawn to limitations of [3H]NE kinetics.