Neuronal and extraneuronal uptake of norepinephrine in the human forearm.
The effect of the neuronal uptake (U1) inhibiting drug desmethylimipramine (DMI) and the extraneuronal uptake (U2) inhibiting drug hydrocortisone (HC) upon the forearm extraction (FE) of norepinephrine (NE) was investigated in six healthy male subjects. Four infusions of NE 0.2 ng/kg per min were given intra-arterially (i.a.) concomitantly with three doses of DMI and subsequently with three doses of HC combined with one dose of DMI. All doses of DMI and the highest two doses of HC decreased the FE of NE significantly. As a result of local U1 and possibly also U2 inhibition, the venous-arterial plasma NE difference over the forearm increased between the start of the first infusion and the start of the last infusion, indicating an important degree of local neuronal release of NE in basal conditions. It is concluded that the extensive removal of NE by U1 and U2, and the local release of NE limit the use of peripheral venous NE concentration as a measure of overall sympathetic activity.
Chang
P C
PC
Department of Nephrology, University Hospital, Leiden, The Netherlands.
van Brummelen
P
P
Vermeij
P
P
van der Krogt
J A
JA
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D005542:Forearm / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology
D003891:Desipramine; D006854:Hydrocortisone; D009638:Norepinephrine