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

Abstract

To assess sympathetic nervous system function in essential hypertension, we measured the rates of release to and removal from plasma of the sympathetic neurotransmitter, norepinephrine. In normal subjects, disappearance of tritiated l-norepinephrlne from plasma, after infusion to steady state, was biexponential, with t1½ = 2.0 ± 0.4 minutes (mean ± standard deviation) and t1½ = 33 ± 15 minutes. The rapid component of removal seemed to represent neuronal uptake of norepinephrine: the t1½ 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, the t1,½ 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 the rate of spillover of norepinephrine to plasma, of transmitter escaping uptake after release, was 0.73 ± 0.39 μg/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. © 1981 American Heart Association, Inc.