Plasma concentrations of noradrenaline and 3,4-dihydroxyphenylethyleneglycol under conditions of enhanced sympathetic activity

Abstract

Antecubital venous blood was sampled at rest and during orthostasis or supine bicycle exercise. The plasma was analyzed for noradrenaline and 3,4-dihydroxyphenylethyleneglycol (DOPEG) by HPLC. Orthostasis resulted in increases in plasma concentrations of both noradrenaline and DOPEG. The magnitude of changes in both was dependent on the degree of orthostasis. In conditions of supine rest, sitting, and standing the plot of the geometric mean values of plasma DOPEG (ordinate) against those of plasma noradrenaline was linear, had a slope of about unity, and intersected the ordinate at a finite value of plasma DOPEG. After administration of desipramine (to block uptake₁), plasma concentrations of DOPEG fell both at rest and during orthostasis. Moreover, desipramine abolished the plasma DOPEG response to orthostasis without affecting the plasma noradrenaline response. Hence, changes in plasma DOPEG brought about by changes in sympathetic tone are presynaptic in origin. The plasma concentration of DOPEG observed in the presence of desipramine was virtually identical with the ordinate intercept of the regression line relating plasma DOPEG to plasma noradrenaline in the absence of desipramine. This pool of plasma DOPEG (which amounted to about 75% of that observed at supine rest in the absence of desipramine) probably stems from intraneuronal noradrenaline leaking out of the storage vesicles of peripheral sympathetic neurones and may in part also be derived from the central nervous system. Supine bicycle exercise failed to increase plasma DOPEG. This may be due to the separation of the sampling site from the site of noradrenaline release (i.e. the exercising limbs) by organs involved in DOPEG extraction. The failure of plasma DOPEG to rise under these conditions may also be a consequence of increased blood flow in the exercising limbs, resulting in a marked decrease in the proportion of the released noradrenaline being recaptured by the sympathetic nerve endings.