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 alpha(2)-adrenoceptors in the nucleus reticularis gigantocellularis (NRGC) of the medulla oblongata involved in cardiovascular regulation. Adult, male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. supplements) were used. The circulatory suppressant efficacy of a centrally acting alpha(2)-adrenoceptor agonist, guanabenz, was used as the experimental index. Bilateral microinjection of SP (300 or 600 pmol) into the NRGC, a medullary site that is critically involved in the cardiovascular depressive actions of guanabenz, significantly diminished the hypotensive and bradycardiac efficacy of the aminoguanidine compound (100 mu g/kg, i.v.). This implied reduction in alpha(2)-adrenoceptor activity in the NRGC by SP was antagonized by its selective receptor antagonist, [D-Pro(2),D-Trp(7,9)]-SP (1200 pmol). Similarly, attenuation by SP of the cardiovascular suppressant effects of guanabenz was also reversed by immunocytochemically verified depletion of dopamine-beta-hydroxylase-immunoreactive nerve terminals in the NRGC, elicited by the selective noradrenergic neurotoxin, DSP4 (50 mu g) These data suggest that SP may exert an inhibitory action on the alpha(2)-adrenoceptors in the NRGC that are involved in central cardiovascular regulation, possibly via a presynaptic modulation on noradrenergic neurotransmission.