Participation of Noradrenergic Neurotransmission in the Enhancement of Baroreceptor Reflex Response by Substance P at the Nucleus Tractus Solitarii of the Rat: A Reverse Microdialysis Study

We applied reverse microdialysis and HPLC analysis to evaluate the participation of noradrenergic neurotransmission in modulation of the baroreceptor reflex response by substance P at the nucleus tractus solitarii in Sprague-Dawley rats anesthetized with pentobarbital sodium (50 mg/kg, i.p., with 20 mg/kg/h.i.v. supplement). Continuous infusion of substance P (600 microM) at 1 microliter/min into the nucleus tractus solitarii through a stereotaxically positioned microdialysis probe (active exchange length, 180-200 microns; diameter, 220 microns) for 1 h elicited an enhancement of the baroreceptor reflex response. This facilitatory effect correlated positively, during the 60-min infusion period, with the time course of increase in the extracellular concentration of substance P and noradrenaline in the nucleus tractus solitarii. Experimentally elevating the concentration of noradrenaline at this medullary nucleus also augmented the baroreceptor reflex sensitivity. On the other hand, depletion of the noradrenergic fibers and nerve terminals at the nucleus tractus solitarii with DSP4 diminished the enhancement of baroreceptor reflex response and the corresponding elevation in extracellular concentration of noradrenaline by substance P. Microinfusion of noradrenaline into the nucleus tractus solitarii in DSP4-treated animals, however, potentiated the baroreceptor reflex response. These results suggested that the enhancement of baroreceptor reflex response by substance P may involve an increase in the concentration of noradrenaline at the nucleus tractus solitarii via a presynaptic mechanism.