SUBSTANCE-P SUPPRESSES THE ACTIVITY OF ALPHA(2)-ADRENOCEPTORS OF THE NUCLEUS-RETICULARIS GIGANTOCELLULARIS INVOLVED IN CARDIOVASCULAR REGULATION IN THE RAT

We evaluated possible interactions between substance P (SP) and the al pha(2)-adrenoceptors in the nucleus reticularis gigantocellularis (NRG C) of the medulla oblongata involved in cardiovascular regulation. Adu lt, male Sprague-Dawley rats anesthetized with pentobarbital sodium (4 0 mg/kg, i.p., with 10 mg/kg/h i.v. supplements) were used. The circul atory suppressant efficacy of a centrally acting alpha(2)-adrenoceptor agonist, guanabenz, was used as the experimental index. Bilateral mic roinjection of SP (300 or 600 pmol) into the NRGC, a medullary site th at is critically involved in the cardiovascular depressive actions of guanabenz, significantly diminished the hypotensive and bradycardiac e fficacy of the aminoguanidine compound (100 mu g/kg, i.v.). This impli ed reduction in alpha(2)-adrenoceptor activity in the NRGC by SP was a ntagonized by its selective receptor antagonist, [D-Pro(2),D-Trp(7,9)] -SP (1200 pmol). Similarly, attenuation by SP of the cardiovascular su ppressant effects of guanabenz was also reversed by immunocytochemical ly verified depletion of dopamine-beta-hydroxylase-immunoreactive nerv e terminals in the NRGC, elicited by the selective noradrenergic neuro toxin, DSP4 (50 mu g) These data suggest that SP may exert an inhibito ry action on the alpha(2)-adrenoceptors in the NRGC that are involved in central cardiovascular regulation, possibly via a presynaptic modul ation on noradrenergic neurotransmission.