Handling of tracer norepinephrine by the dog liver

Norepinephrine handling by the dog liver was appraised by carrying out tracer-transient, multiple-indicator-dilution studies within steady-state conditions in a basal situation, during norepinephrine infusion and after the uptake inhibitor desipramine. In controls, tracer norepinephrine extraction averaged 61%, whereas bulk norepinephrine extraction was approximately 31%; intrahepatic secretion of unlabeled norepinephrine accounted for the difference. Infusion of norepinephrine, raising arterial levels more than an order of magnitude, constricted the hepatic vascular space but did not change tracer extraction; norepinephrine secretion remained essentially unchanged, and with this, bulk extraction approached tracer extraction. A theoretical analysis of norepinephrine uptake was developed. Analysis of tracer data with this indicated that the permeability surface products for influx and efflux, expressed per gram liver, did not change. Desipramine did not affect the uptake kinetics, indicating that the uptake process was virtually completely nonneurogenic. Late efflux of tracer normetanephrine product was detected but was small prior to recirculation. The study demonstrates that norepinephrine secretion ordinarily coexists with uptake and provides an approach to quantitating both.