Comparison of two indices for forearm noradrenaline release in humans

Although there is as yet no method which measures directly the neuronal rel ease of noradrenaline in humans in vivo, the isotope dilution technique wit h [H-3]noradrenaline has been applied to estimate forearm neuronal noradren aline release into plasma. Two different equations have been developed for this purpose: one to estimate the spillover of noradrenaline into the venou s effluent, and a modified formula (often referred to as the appearance rat e) which may reflect more closely changes in the neuronal release of noradr enaline into the synaptic cleft, particularly during interventions that alt er forearm blood flow. The present study was performed to compare the effec ts of two interventions known to exert contrasting actions on neuronal fore arm noradrenaline release and forearm blood flow. Intra-arterial infusion o f sodium nitroprusside at doses without systemic effect increases forearm b lood flow, but not neuronal noradrenaline release. in contrast, lower-body negative pressure at -25 mm Hg causes forearm vasoconstriction by stimulati ng neuronal noradrenaline release. During sodium nitroprusside infusion, fo rearm noradrenaline spillover increased from 11 +/- 0.3 to 2.2 +/- 1.0 pmol .min(-1) 100 ml(-1) (P < 0.05), whereas the forearm noradrenaline appearanc e rate was unchanged. Lower-body negative pressure did not affect the forea rm noradrenaline spillover rate, but increased the forearm noradrenaline ap pearance rate from 3.4 +/- 0.4 pmol.min(-1).100 ml(-1) at baseline to 5.0 /- 0.9 pmol.min(-1).100 ml(-1) (P < 0.05). These results indicate that the noradrenaline appearance rate provides the better approximation of changes in forearm neuronal noradrenaline release in response to stimuli which alte r local blood flow.