Estimation of sympathetic activity in essential hypertension The estimation of sympathetic nervous activity by measurement of plasma norepinephrine (NE) concentration ass~irnes a constant relation between this and the synaptic cleft concentration. This ass~~mption would be incorrect if the clearance of plasrna NE could be varied without affecting its removal from the synaptic clcft, so we compared the clearance of plasma NE in mild hypertensives and norrnul subjects by measurement of its plasma concentrution during a 0.5-hr irlfusion at 0.07 pglkglmin; there were no d~fsc~ences. The simultaneous infusion of isoproterenol, 0.02 pglkglmin, led to an increase in heart rate and NE clearance. There ~vas purtial inhibition qf catechol-0-methyltransferuse by a single oral dose ($'alpha-methyldopa, 250 rng, which reduced the clearance of' both cutec~holamines (CAs) by about 20%. After the end of the infusions containing isoproterenol, the tachycardia persisted for more than 1 hr and declined rnore slowly in the hypertensives than the normals. In contrast, plasma concentrations qf both CAs returned to basal values within a few minutes. The persistent tachycardiu may be due to rerelease qf' isoproterelzol into the synaptic cl@, since stirnulation of symnpathetic activity by assumption ofthe erect posture was associated with an exaggerated increase in heart rate (by 48lmin after infusion and 23lmin hcfore infusion). The study therefore suggests that synaptic clcfi and plasrna CA concentrations can he independently manipulated and the relation between them may be different in hypertensive patients and normal control subjects. M. J. Brown, M.B., F. J. M. Lhoste, M.D., C. Zamboulis, M.D., P. W. Ind, M.B., D. A. Jenner, M.Sc., and C. T. Dollery, M.B. London, Englat~d Department of Clinical Pharmacology, Royal Postgraduate Medical School Despite many studies of plasma catecholamine (CA) levels in patients with essential hyperten- sion, there is still little agreement whether in- creased sympathetic nervous activity is of importance in the pathogenesis of hyperten- sion.& 10, 1 I, 20, 26, 27, 30, 31, 33. 3-1 A less studied but fundamental problem is whether plasma CA measurements are a valid index of sympathetic Supported by Medical Research Council grant No. G979164615. Received for publication April 8, 198 1. Accepted for publication Sept. 10, 198 1. Reprint requests to: M. J. Brown, Department of Clinical Phar- macology, Royal Postgraduate School of Medicine, Ducane Rd., London W 12 OHS, England. activity in comparisons between individuals or groups who may not share a similar relation between their synaptic cleft and plasma CA con- centrations. Both of these are the net result of release rate and clearance. The removal of CAs from the synaptic cleft is predominantly by neuronal ''reuptake ' '(uptake,), while other path- ways-catechol-0-methyltransferase (COMT) and extraneuronal uptake-may be of similar importance in the clearance of plasma C A S . ~ ~ If any of these pathways were impaired in hyper- tension, the relation of synaptic cleft to plasma CA concentration would be altered. In some studies of norepinephrine (NE) in essential hypertension, clearance has been found 16 0009-92361821010016+07$00.70/0 0 1982 The C. V. Mosby Co.