The possible interaction of glutamatergic metabotropic agonists and N-methyl-d-aspartate (NMDA) receptors was investigated in the nucleus tractus solitarii (NTS) of awake rats. The cardiovascular responses to unilateral microinjection of trans-1-amino-1,3-cyclopentanediocarboxylic acid (trans-ACPD; 250 pmol/50 nL) into the NTS (n= 8) produced hypotension (-64 +/- 4 mmHg) and bradycardic (-206 +/- 11 bpm) responses, which were blocked by previous microinjection of 2-amino-5-phosphonovaleric acid (AP-5; 10 nmol/50 nL), a selective antagonist of NMDA ionotropic receptors, into the same site. Intravenous injection of methyl-atropine blocked both the bradycardic and hypotensive responses to microinjection of trans-ACPD into the NTS, indicating that the hypotension was secondary to the intense bradycardic response. The data also showed that the bradycardic and hypotensive responses to microinjection of an NMDA agonist (10 pmol/50 nL) into the NTS were not affected by previous microinjection of alpha-methyl-4-carboxyphenylglycine (MCPG; 5 nmol/50 nL), a non-selective antagonist of metabotropic receptors. The results showing that the cardiovascular responses to microinjection of trans-ACPD into the NTS were blocked by AP-5 indicate that the responses to metabotropic agonists in the NTS involves NMDA receptors.