P. Leonard

Determination of norepinephrine apparent release rate and clearance in humans.

A method for estimating the rate of entry of norepinephrine into plasma (norepinephrine apparent release rate) and clearance of norepinephrine from plasma in humans is presented. The procedure involves the intravenous infusion of tritiated l-norepinephrine, of sufficiently high specific activity to avoid elevating blood pressure, until plateau concentration is reached in plasma, and measurement of norepinephrine specific activity under steady state conditions. In ten normal subjects at rest, the apparent release rate of norepinephrine was 0.54 ± 0.20 μg/m2/min. (mean ± standard deviation). It was significantly lower in four patients with idiopathic peripheral autonomic insufficiency, 0.19 ± 0.12 μg/m2/min., but in the latter, despite reduced norepinephrine release, plasma norepinephrine concentration was near normal because of slowed clearance of norepinephrine from the circulation, 1.69 ± 0.44 l/min. compared with 2.80 ± 0.73 l/min. in normal subjects (p<0.05). In four normal subjects given the norepinephrine uptake inhibitor, desipramine, to slow removal of norepinephrine from the circulation, again the plasma concentration of neurotransmitter was higher than would be expected from the existing apparent release rate of norepinephrine. The findings suggest that methods which measure the dynamic processes of norepinephrine release and removal quantify sympathetic nervous activity better than steady state plasma norepinephrine measurements alone.

Noradrenaline turnover during under- and over-eating in normal weight subjects☆

Adjustments to sympathetic nervous system activity may regulate constant body weight despite wide variations in energy intake. To test this six normal weight subjects were studied at three different energy intakes (low, weight maintaining and high). Noradrenaline turnover was measured on the tenth day of each diet. Both noradrenaline appearance rate and noradrenaline clearance increased significantly with increasing energy intake and were a more sensitive indices than the plasma noradrenaline concentrations which rose, but not significantly. Fasting triiodothyronine (T3) rose and reverse T3 fell with increasing energy intake, while thyroxine (T4) concentrations did not change. Systolic blood pressure also rose significantly. Underfeeding resulted in reductions in noradrenaline appearance and clearance rates and in the T3 level. These results demonstrate that sympathetic nervous system activity, as determined by noradrenaline turnover in plasma, varies in response to short-term changes in energy intake in normal weight subjects. These changes may partly explain why some individuals maintain body weight constant despite large differences in food intake. The present findings may also be relevant to the variability in susceptibility to become obese.

Norepinephrine kinetics in essential hypertension. Defective neuronal uptake of norepinephrine in some patients.

SUMMARY To assess sympathetic nervous system function in essential hypertension, we measured tbe rates of release to and removal from plasma of the sympathetic neurorransmltter, norepinephrine. In normal subjects, disappearance of tritiated /-norepinephrlne from plasma, after infusion to steady state, was biexponential, with

Effect of norepinephrine uptake blockers on norepinephrine kinetics

= 2.0 ± 0.4 minutes (mean ± standard deviation) and

TOTAL, AND ORGAN-SPECIFIC, NORADRENALINE PLASMA KINETICS IN ESSENTIAL HYPERTENSION

= 33 ± 15 minutes. Tbe rapid component of removal seemed to represent neuronal uptake of norepinephrine: the

Biochemical quantification of sympathetic nervous activity in humans using radiotracer methodology: fallibility of plasma noradrenaline measurements

was lengthened by the selective inhibitor of neuronal norepinephrine uptake, desipramine; it was not changed by the extraneuronal uptake blocker, cortlsol; and it was prolonged in patients with peripheral sympathetic nerve dysfunction (idiopathic autonoroic insufficiency). In eight of 37 hypertensive patients, tbe