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 participation of noradrenergic neurotransmission in the modulation by substance P of alpha 2-adrenoceptors at the nucleus reticularis gigantocellularis involved in cardiovascular regulation, using Sprague-Dawley rats anesthetized with pentobarbital sodium. The efficacy of circulatory suppression of a centrally acting alpha 2-adrenoceptor agonist, guanabenz, was used as the experimental index. Continuous infusion of substance P (600 or 1200 pmol/microliters/min) into the nucleus reticularis gigantocellularis through a stereotaxically positioned microdialysis probe (active exchange length: 500 microns, diameter: 220 microns) for 80 min elicited a reduction in the hypotensive and bradycardiac actions of guanabenz (100 micrograms/kg, i.v.). This implied suppression of alpha 2-adrenoceptor activity correlated positively with the time-course of increase in the estimated extracellular concentration of the undecapeptide and norepinephrine in the nucleus reticularis gigantocellularis. Experimentally 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 compound. These results suggest that substance P may depress the activity of the alpha 2-adrenoceptors in the nucleus reticularis gigantocellularis that are involved in central cardiovascular regulation via an increase in the extracellular concentration of norepinephrine at this reticular nucleus.
Tsou
M Y
MY
Department of Anesthesiology, Veterans General Hospital-Taipei, Taiwan, ROC.
Len
W B
WB
Lee
T Y
TY
Chan
S H
SH
Pan
W H
WH
Chan
J Y
JY
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D006143:Guanabenz / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D008845:Microinjections; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012154:Reticular Formation / Q000502:physiology*; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D013373:Substance P; D006143:Guanabenz; D009638:Norepinephrine