1. The validity of plasma noradrenaline as an index of sympathetic nervous activity was assessed by estimating variation in individual organ contribution to circulating concentrations.2. Arteriovenous (A-V) differences in noradrenaline and adrenaline concentration were measured across several organs in nine patients with mild essential hypertension, in five with renal artery stenosis and 15 phaeochromocytoma patients.3. In patients with phaeochromocytomas the percentage extraction of noradrenaline and adrenaline (estimated from the A-V differences) was similar across all organs, suggesting that adrenaline extraction could be used as a marker for noradrenaline extraction.4. In the non-tumour patients the A-V difference for noradrenaline was less than that for adrenaline across most organs studied, reflecting the net result of noradrenaline release and extraction. The estimated contribution of various organs to the noradrenaline concentrations in their venous effluent was: heart. 21%; kidney 47%; legs 68%.5. This pattern of A-V difference proved a positive diagnostic feature for non-tumour patients since it was not found even in the patients with small phaeochromocytomas, whose peripheral venous noradrenaline concentration alone did not distinguish them. Correspondence: Dr M. J. Brown, Department of Clinical Pharmacology, Royal Postgraduate Medical School, Du Cane Road, London W12 OHS.6. The venous-arterial difference across the adrenal. glands of non-tumour patients was more than 10-fold greater for adrenaline than that for noradrenaline. Since the mean arterial concentration of noradrenaline was more than fivefold higher than that of adrenaline, the normal adrenal contribution to circulating noradrenaline is likely to be less than 2%. 7. In the patients with renal artery stenosis renal venous concentrations of noradrenaline (from the ischaemic kidney) were higher than arterial values, but mean arterial values were no higher than in the essential hypertensive patients.8. Local variations in sympathetic activity may occur without altering the plasma noradrenaline concentration measured in peripheral plasma.

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The rate constant (alpha2) of the terminal exponential of the technetium-99m diethylene triamine penta-acetic acid (DTPA) plasma clearance curve is close to the ratio of glomerular filtration rate (GFR) to extracellular fluid volume (ECV) and is therefore a convenient, already normalised, measure of filtration function. Since alpha2 depends on the distribution volume of the tracer, our aim was to compare alpha2 from inulin and 99mTc-DTPA and also to compare the equilibration kinetics of the two filtration markers. Fifty millilitres of 99mTc-DTPA (250MBq) and inulin (10%), mixed in the same syringe, were given by intravenous injection in 15 patients undergoing routine 99mTc-DTPA renography for a variety of clinical indications. Frequent antecubital venous blood samples were taken up to about 4h after injection to construct plasma clearance curves from which GFR, ECV and GFR/ECV (i.e. the reciprocal of mean transit time through the distribution volume) were calculated. 99mTc-DTPA/inulin concentration ratio curves were also constructed after normalisation to the ratio in the syringe. GFR given by the two markers correlated closely (DTPA=0.98.inulin-0.4ml/min; r=0.98). 99mTc-DTPA had the same distribution volume as inulin, had a similar transit time through it and gave the same value of alpha2 (r=0.98). GFR/ECV from 99mTc-DTPA accordingly correlated closely with GFR/ECV from inulin (DTPA=0.75.inulin+0.99 ml/min; r=0.95). Even though the distribution volumes and the times to equilibration (i.e. to reach the terminal exponential) were similar, the distribution volume of 99mTc-DTPA at about 10min after injection was, after subtraction of the plasma volume, about twice that of inulin. We confirm the validity of 99mTc-DTPA for measuring GFR. alpha2 is a convenient measure of GFR, can be based on the terminal exponential of inulin of 99mTc-DTPA curves and can be converted to GFR/ECV with an appropriate scaling factor. The kinetics or the two clearance curves with respect to anatomical correlates of the exponentials and the rates of diffusion throughout the respective distribution volumes requires further study.

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