Effects of propofol on desipramine-sensitive [3H]-noradrenaline uptake kinetics in rat femoral artery.
BACKGROUND
The intravenous anaesthetic propofol inhibits the neuronal uptake of noradrenaline (uptake1) from the vascular sympathetic neuromuscular junction, resulting in an enhancement of the sympathetic neurotransmission. This could be important for maintenance of blood pressure during propofol anaesthesia. The aim of the present study was to determine how propofol influences the kinetics of uptake1.


METHODS
Isolated segments of rat femoral arteries were incubated with [3H]-noradrenaline in the presence or absence of propofol and the radioactivity taken up was measured in a scintillation counter. The uptake1 inhibitor, desipramine, was used to delineate the specific neuronal uptake.


RESULTS
Desipramine and 10 microM propofol significantly reduced the uptake in segments incubated with 0.1 microM [3H]-noradrenaline. Propofol at 1 microM and 100 microM did not affect the uptake. Non-linear regression analysis of specific uptake yielded Km 0.50 microM, Vmax 1.6 pmol mg(-1) 15 min(-1) and Hill coefficient 1.1. Propofol (1-10 microM) increased the Km value and propofol (10-100 microM) increased the Vmax value concentration-dependently, while the Hill coefficient was not affected.


CONCLUSIONS
Propofol seems to have a biphasic effect on the uptake of noradrenaline in the vascular sympathetic neuromuscular junction. At lower propofol concentrations there is a decrease in the affinity of the noradrenaline transporters. The resulting uptake inhibition is counteracted at higher propofol concentrations by an increase in the efficacy of the uptake.
Sandström
K
K
Department of Anaesthesia and Intensive Care, University Hospital, Lund, Sweden.
Wallerstedt
S M
SM
Tornebrandt
K
K
Bodelsson
M
M
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000465:Algorithms; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D003891:Desipramine / Q000494:pharmacology*; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009638:Norepinephrine / Q000493:pharmacokinetics*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000493:pharmacokinetics*
D018759:Adrenergic Uptake Inhibitors; D018686:Anesthetics, Intravenous; D014662:Vasoconstrictor Agents; D003891:Desipramine; D009638:Norepinephrine; D015742:Propofol