G.P. Jackman

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.

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

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

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

Effects of noradrenergic neuronal activity on 3,4-dihydroxyphenylethylene glycol (DHPG) levels. Quantitation by high performance liquid chromatography

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

No stereoselective first‐pass hepatic extraction of propranolol

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

Evidence for a predominantly central hypotensive effect of alpha-methyldopa in humans.

was > 2.8 minutes (range, 3.3-6.0 min), longer than in any normal subject; this appears to be presumptive evidence of the existence of defective neuronal norepinephrine uptake. In these patients tbe rate of spillover of norepinephrine to plasma, of transmitter escaping uptake after release, was 0.73 ± 0.39 Mg/m2/min (43 ± 23 ninoles/m2/min), higher than in normal subjects, 036 ± 0.14 ng/m2/mia (2.1 ± 0.8 nmoles/m2/min) (p < 0.01). A defect in neuronal uptake of norepinephrine, by exposing adrenergic receptors to high local norepinephrine concentration, may be important in the parhogenesis of blood pressure elevation in some patients with essential hypertension.