AJP - Endocrinology and Metabolism, Vol 257, Issue 5 E743-E750, Copyright © 1989 by American Physiological Society
Plasma norepinephrine in humans: limitations in assessment of whole body norepinephrine kinetics and plasma clearance
J. H. Henriksen and N. J. Christensen
Department of Clinical Physiology, Hvidovre Hospital, Denmark.
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.
