Estimation of noradrenaline concentrations in the axoplasm of noradrenergic neurones in man

Abstract

The plasma concentrations of noradrenaline (NA) and its primary neuronal metabolite, dihydroxyphenylglycol (DOPEG), were examined during graded orthostasis and NA infusion in 13 healthy subjects to estimate the NA concentration difference between the site of neuronal DOPEG formation and that in plasma. Stimulation of NA release by graded orthostasis resulted in similar absolute increments in plasma NA and DOPEG with both plasma concentrations being dependent on the degree of orthostasis. The mean value of the delta DOPEG/delta NA ratio amounted to 0.999 (0.745; 1.341). NA was infused i.v. during two consecutive 30-min periods at constant rates of 0.43 and 0.86 nmol kg-1 min-1, respectively. This infusion resulted in a delta DOPEG/delta NA ratio of 0.048 (0.036; 0.064) for the first and 0.078 (0.067; 0.090) for the second infusion period (p less than 0.01). For each individual subject, the factor quantifying the NA concentration difference between the site of neuronal DOPEG formation and plasma was calculated from the square root of the ratio of 'delta DOPEG/delta NA during orthostasis to delta DOPEG/delta NA during the low rate of NA infusion'. The average NA concentration at the site of neuronal DOPEG formation (i.e. the axoplasm of noradrenergic neurones) was found to be 4.6-fold higher than that in plasma.