Norepinephrine removal and release in the forearm of healthy subjects.

Abstract

SUMMARY The relevance of local removal and release of norepinephrine (NE) for antecubital venous plasma NE concentration was studied in 22 healthy subjects. Arterial and venous plasma NE and forearm blood flow were measured during 1) intra-arterial infusion of two doses of NE, 2) intraarterial NE infusion with two doses of sodium nitroprusside, 3) intravenous infusion of NE with intraarterial infusion of four doses of sodium nitroprusside, and 4) lower body negative pressure of -2 0 mm Hg for 15 minutes. The venous plasma NE concentration-time curves during the infusions of the two doses of NE indicated first-order kinetics for forearm extraction: forearm NE extraction rate during the low dose infusion was 67 ± 4.1% (SEM) and correlated with basal forearm blood flow (r= -0.64, p<0.03, n= 12). Local sodium nitroprusside-induced vasodilatation during the intraarterial and intravenous NE infusions was accompanied by dose-dependent decreases in forearm extraction rates for NE and epinephrine. During lower body negative pressure, taking into account the high basal forearm extraction rate for NE, local and systemic release of NE was indicated by increases in arterial and venous plasma and the venous-arterial plasma NE concentration difference (p<0.05 for all). These data show that removal of NE from forearm circulation is a process with a high extraction ratio obeying first-order kinetics and that this extraction process inversely relates to forearm blood flow. Thus, antecubital venous plasma NE is likely to be derived mainly from local release and not from the arterial plasma NE input. (Hypertension 8: 801-809, 1986) KEY WORDS * plasma norepinephrine • plasma epinephrine • norepinephrine release norepinephrine extraction • epinephrine extraction • forearm blood flow • sodium nitroprusside • lower body negative pressure T HE plasma norepinephrine (PNE) concentration in blood taken from a forearm vein is a widely used estimate of overall sympathetic nervous system activity. Although several studies have shown a correlation between venous PNE and the activity of the sympathetic nervous system, 1 " 3 this approach has also been criticized. 4 -5 For instance, Mancia et al. 6 showed that alterations in sympathetic tone and blood pressure induced by manipulating the baroreflex were not reflected by alterations in plasma catecholamine concentrations. Also, during experimental mental stress, changes in sympathetic nerve activity are not paralleled by changes in venous PNE. From the Depts. of Nephrology

Aftereffects of exercise on regional and systemic hemodynamics in hypertension.

“…These observations are related to plasma norepinephrine concentrations. Indeed, it has been shown that antecubital venous plasma norepinephrine is derived mainly from local release in the forearm 20 and that skeletal muscle vascular beds are a major source of circulating norepinephrine, whereas skin contributes to a lesser extent. 21 In the present study, the observation that plasma norepinephrine concentrations were decreased together with forearm vascular resistance from 30 to 90 minutes after exercise in hypertensive subjects and that both norepinephrine and forearm hemodynamics were unchanged in normotensive individuals is consistent with the hypothesis that sympathetic nervous activity to skeletal muscle vascular beds is reduced after exercise in hypertensive subjects.…”

Prejunctional angiotensin II receptors. Facilitation of norepinephrine release in the human forearm.

“…The key to our success in demonstrating this effect was to markedly increase forearm blood flow by concomitantly infusing intraarterial nitroprusside. This served to eliminate the following three factors which might mask the Ang II facilitation ofNE release: (a) decreased NE release via stimulation of prejunctional alpha2 adrenergic receptors by higher concentrations of NE in the synaptic cleft; (b) neuronal reuptake of the excess released NE; and (c) an Ang II-mediated decrease in regional blood flow which retards NE washout into the circulation (35 of the mechanisms by which ACE inhibitor therapy produces its beneficial effects in CHF is on blocking Ang II-facilitated NE release under conditions of stress, thereby lessening the toxic effects of NE on the heart and circulation. However, further studies would be required to prove this conclusively.…”

“…We used [3H] NE kinetic methodology to examine the effects of Ang II on forearm as well as systemic NE spillover and clearance (34). We also maintained a markedly increased forearm blood flow by the simultaneous intraarterial infusion of nitroprusside to facilitate NE washout into the circulation (35) and to minimize the masking of an effect by local modulating factors such as neuronal NE reuptake and prejunctional alpha2 autoinhibition.…”

Effects of Risperidone on the Peripheral Noradrenegic System in Patients with Schizophrenia A Comparison with Clozapine and Placebo

“…In particular, the differences in the source of the NE sample may be crucial because NE concentrations in antecubital venous blood may be unreliable indicators of total body sympathetic nervous activity (Folkow et al 1983). An advantage of arterial sampling is independence from local peripheral metabolism and blood flow, as suggested by studies demonstrating that tissues of the arm remove a substantial proportion of the radioactively-labeled NE in the arterial plasma (Chang et al 1986).…”