Metabolism of D, L-3H-Norepinephrine in Essential Hypertension

Abstract

Defective control of the cardiovascular system by the sympathetic nerves continues to be incriminated as the potential primary physiologic defect in essential hypertension (EH). The need to measure sympathetic tone has progressed from physiologic mensuration by assessment of reflex and pharmacological responses to the recent assay of norepinephrine (NE) and its congeners in both urine and plasma. The way in which the body handles D,L-B-³H-NE represents yet another technique by which to evaluate sympathetic function. Previous studies of EH by this method demonstrated more rapid plasma disappearance of ³H-NE as well as elevated 24 hour tritium accumulation in the urine following D,L-B-³H-NE injection. The present study of 7 normotensive subjects and 7 patients with EH was designed to depict more precisely these abnormalities in ³H-NE metabolism. Following a one minute injection of 8 μg D,L-B-³H-NE, (200 μCi) intravenously, the excretion of unlabeled endogenous metabolites and their labeled congeners was assayed. By these means one could estimate catecholamine synthesis, turnover of the labeled pools, and by comparison of relative specific activities of the metabolites, gain some insight into the distribution of the injected material. Alternative catabolic pathways were evaluated by measurement of the excretion of ³H₂O. Patients with EH excreted more label per 24 hours, revealed a more rapid decline of ³H₂O excretion and lower specific activity of normetanephrine (NM). These findings are compatible with changes in pool dynamics and distribution of administered label which gave additional support to the concept of adrenergic dysfunction in association with essential hypertension.