A KINETIC STUDY OF THE DISPOSITION OF CIRCULATING NOREPINEPHRINE IN NORMAL MALE SUBJECTS

¹ Illinois State Psychiatric Institute, Chicago, Illinois

Seven physically healthy, young men were infused, continuously, with dl--H³-norepinephrine (NE) (specific activity, 8.521 ± 0.319 c/mM) at the rate of 1.92 µc/hr for a 48-hour period, and urine specimens were collected throughout the period of infusion as well as afterward. Data is presented which suggests that the infusion did not perturb the system under study and that by the latter part of the infusion homogeneous mixing with those pools with which the circulating free NE is normally in equilibrium had occurred. The rates of appearance and disappearance of free H³-NE in urine are noted and used to obtain solutions for a kinetic model which represents the disposition of NE released from sympathetic nerve endings into the circulation. From these solutions it is estimated that in the normal subject approximately 911 µg of metabolites due to breakdown of NE released at nerve endings are formed per 24 hours which constitutes 25% of the catecholamine breakdown products excreted in urine per 24 hours. It is concluded that in the human subject the bulk of the total pool of metabolites excreted into urine has its origin in intracellular metabolism without prior release at nerve endings. For every microgram of circulating free NE excreted into urine during a 24-hour period 35 µg are excreted as metabolic products which indicates that urinary levels of free NE in the healthy male represent approximately 2.5% to 3% of the NE released into the circulation from nerve endings. It is noted that the biphasic plot of the appearance of H³-NE in urine is consistent with the behavior of an isotopically traced system in which extracellular NE is concentrated in intracellular pools against a gradient and as such cannot be taken as evidence for the existence of two pools of NE which are turning over at different rates. It is estimated that the free NE present in the extracellular pools and those intracellular pools with which the extracellular NE is in equilibrium has a single turnover time of 10.10 hours, i.e., a biologic half-life of approximately 5.0 hours.

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