Effects of propofol on desipramine-sensitive [H-3]-noradrenaline uptake kinetics in rat femoral artery

Background: The intravenous anaesthetic propofol inhibits the neuronal upta ke of noradrenaline (uptake(1)) 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 in fluences the kinetics of uptake(1). Methods: Isolated segments of rat femoral arteries were incubated with [H-3 ]-noradrenaline in the presence or absence of propofol and the radioactivit y taken up was measured in a scintillation counter. The uptake, inhibitor, desipramine, was used to delineate the specific neuronal uptake. Results: Desipramine and 10 mu M propofol significantly reduced the uptake in segments incubated with 0.1 mu M [3H]-noradrenaline. Propofol at 1 mu M and 100 mu M did not affect the uptake. Non-linear regression analysis of s pecific uptake yielded K-m 0.50 mu M, V-max 1.6 pmol mg(-1) 15 min(-1) and Hill coefficient 1.1. Propofol (1-10 mu M) increased the K-m value and prop ofol (10-100 mu M) increased the V-max value concentration-dependently, whi le the Hill coefficient was not affected. Conclusion: Propofol seems to have a biphasic effect on the uptake of norad renaline in the vascular sympathetic neuromuscular junction. At lower propo fol concentrations there is a decrease in the affinity of the noradrenaline transporters. The resulting uptake inhibition is counteracted at higher pr opofol concentrations by an increase in the efficacy of the uptake.