Variations in Individual Organ Release of Noradrenaline Measured by An Improved Radioenzymatic Technique; Limitations of Peripheral Venous Measurements in the Assessment of Sympathetic Nervous Activity

Abstract

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.

Catecholamines in arterial and venous umbilical blood: placental extraction, correlation with fetal hypoxia, and transcutaneous partial oxygen tension

“…This was to be anticipated since the metabolic pathways of NE and E are identical. However, a comparison of the placental NE and E extraction with that of other organs revealed that the placental tissue occupies a unique position: on passage of Catecholamines through the liver, cardiac and skeletal muscle, the NE extraction rate is invariably lower than that of E [4,13]. The NE concentrations in the renal vein but also in the coronary sinus may even substantially exceed those measured in the arterial (afferent) blood [21,26].…”

“…Fetal arterial E concentrations as an indicator of enhanced release of the hormone from the adrenal medulla in conditions of stress, also demonstrate good correlations with the fetal parameters, although the correlation coefficients were lower than for NE (Figs. [4][5][6]. Unlike NE and E concentrations, the D levels in the umbilical vessels were affected by fetal hypoxia to a minor degree, only.…”

“…other organs. Hence, the different extraction rates The findings in this study provide a differentiated of NE and E may be taken to reflect the density confirmation of the relationship which exists, of sympathetic innervation and the sympathetic according to LAGERCRANTZ et al [20], between activity of an organ other than the adrenal medulla a tachycardic baseline FHR and total catechola- [4,13,21,26]. In agreement with morphologic mines in the umbilical artery: Our observation studies [30], the nearly identical placental extrac-that an increased baseline FHR is accompanied by tion rates of NE and E indicate that sympathetic a rise of both NE and E concentrations (Fig.…”

Failure of plasma norepinephrine to consistently reflect sympathetic activity in humans.

“…Finally, as Folkow et al 21 caution, activities that increase blood pressure in humans usually do so by effecting differentiated rather than generalized increases in sympathetic discharge. Selective increases in cardiac, renal, or splanchnic sympathetic nerve activity could initiate marked hemodynamic changes in hypertensive persons without altering basal venous PNE concentrations, because of hepatic clearance of catecholamines, 22 regional differences in the vascular response to released norepinephrine, or quantitative differences in the adrenergic innervation to these vascular beds. Indeed, PNE correlates well with efferent sympathetic nerve activity to muscle, 23 an organ unlikely to be involved in the pathogenesis of hypertension.…”

“…22 Furthermore, elevations in renal, splanchnic, or cardiac sympathetic discharge could alter cardiac output or vascular resistance to a much greater extent than PNE concentrations if only a small proportion of circulating norepinephrine comes from these organs. 21 ' 2243 In humans, renal, splanchnic, and cardiac sympathetic nerves together contribute approximately one third of norepinephrine measured in plasma, the lungs another third, and skeletal muscle one fifth.…”