PARTICIPATION OF NORADRENERGIC NEUROTRANSMISSION IN THE SUPPRESSION BY SUBSTANCE-P OF ALPHA(2)-ADRENOCEPTORS AT THE NUCLEUS-RETICULARIS GIGANTOCELLULARIS INVOLVED IN CENTRAL CARDIOVASCULAR REGULATION IN THE RAT

We applied reverse microdialysis and HPLC analysis to quantify the par ticipation of noradrenergic neurotransmission in the modulation by sub stance P of alpha(2)-adrenoceptors at the nucleus reticularis gigantoc ellularis involved in cardiovascular regulation, using Sprague-Dawley rats anesthetized with pentobarbital sodium. The efficacy of circulato ry suppression of a centrally acting alpha(2)-adrenoceptor agonist, gu anabenz, was used as the experimental index. Continuous infusion of su bstance P (600 or 1200 pmol/mu l/min) into the nucleus reticularis gig antocellularis through a stereotaxically positioned microdialysis prob e (active exchange length: 500 mu m, diameter: 220 mu m) for 80 min el icited a reduction in the hypotensive and bradycardiac actions of guan abenz (100 mu g/kg, i.v.). This implied suppression of alpha(2)-adreno ceptor activity correlated positively with the time-course of increase in the estimated extracellular concentration of the undecapeptide and norepinephrine in the nucleus reticularis gigantocellularis. Experime ntally elevating the concentration of norepinephrine at this reticular nucleus via microinfusion by reverse microdialysis also decreased the efficacy of the cardiovascular suppression of the aminoguanidine comp ound. These results suggest that substance P may depress the activity of the alpha(2)-adrenoceptors in the nucleus reticularis gigantocellul aris that are involved in central cardiovascular regulation via an inc rease in the extracellular concentration of norepinephrine at this ret icular nucleus.