We have determined the role of subgroups of metabotropic glutamate receptors (mGluRs) in the nucleus of the solitary tract (NTS) of normotensive Wistar rats. Unilateral microinjection of (S)-3, 5-dihydroxyphenylglycine (3,5-DHPG), an agonist of group I mGluRs, into the NTS significantly decreased mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (-19. 4+/-2.6 mmHg, -16.4+/-5.1 beats/min, and -30.6+/-5.7% by 1 nmol). Microinjection of (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 1 nmol), a putative antagonist of group I mGluRs, into the NTS caused transient decreases in MAP and RSNA, followed by sustained increases in MAP (+8.3+/-2.4 mmHg) and RSNA (+27.7+/-10.8%). Pretreatment with AIDA failed to prevent the cardiovascular and RSNA responses to microinjection of 3,5-DHPG. Unilateral microinjection of (S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG), an agonist of group II mGluRs, into the NTS also significantly decreased MAP, HR, and RSNA, whose responses were not inhibited by pre-microinjection of (2S)-alpha-ethylglutamic acid (EGLU; 2 nmol), a putative antagonist of group II mGluRs. On the other hand, unilateral microinjection of L(+)-2-amino-4-phosphonobutyric acid (L-AP4), an agonist of group III mGluRs, into the NTS caused dose-related decreases in MAP (-8. 3+/-1.5 mmHg by 0.1 nmol and -45.1+/-3.4 mmHg by 0.3 nmol), HR, and RSNA (-21.3+/-3.9% by 0.1 nmol and -77.2+/-6.5% by 0.3 nmol), whose responses were suppressed by pre-microinjection of (R, S)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG; 0.3 nmol), an antagonist of group III mGluRs. These results suggest that all subgroups of mGluRs participate in cardiovascular and sympathetic regulations in the NTS of rats, and that endogenous group I mGluRs in the NTS may contribute to tonic cardiovascular and sympathetic regulations.