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 par ticipation of noradrenergic neurotransmission in modulation of the bar oreceptor reflex response by substance P at the nucleus tractus solita rii 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 mu M) at 1 mu l/min into the nucleus tractus solitari i through a stereotaxically positioned microdialysis probe (active exc hange length, 180-200 mu m; diameter, 220 mu m) for 1 h elicited an en hancement of the baroreceptor reflex response. This facilitatory effec t correlated positively, during the 60-min infusion period, with the t ime 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 nuc leus tractus solitarii with DSP4 diminished the enhancement of barorec eptor reflex response and the corresponding elevation in extracellular concentration of noradrenaline by substance P. Microinfusion of norad renaline into the nucleus tractus solitarii in DSP4-treated animals, h owever, potentiated the baroreceptor reflex response. These results su ggest that the enhancement of baroreceptor reflex response by substanc e P may involve an increase in the concentration of noradrenaline at t he nucleus tractus solitarii via a presynaptic mechanism.