Carbon monoxide has been shown to act as a neurotransmitter and neuronal messenger in the brain. Heme oxygenase catalyzes the conversion of heme to carbon monoxide and biliverdin. We have recently reported that carbon monoxide was involved in central cardiovascular regulation. Carbon monoxide modulated the baroreflex and may affect glutamatergic neurotransmission. In addition, metabotropic glutamate receptors may be coupled to the activation of heme oxygenase in the nucleus tractus solitarii of rats. The present study was designed to investigate the possible interactions of carbon monoxide and metabotropic glutamate receptor groups in the nucleus tractus solitarii. Unilateral microinjection of several agonists for metabotropic glutamate receptor groups such as (R,S)-3,5-dihydroxyphenylglycine (DHPG) (group I) (0.03 nmol), 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (APDC) (group II) (0.3 nmol), and l-(+)-2-amino-4-phosphonobutyric acid (l-AP4) (group III) (0.3 nmol) produced a significant decrease in blood pressure and heart rate. Among the metabotropic glutamate receptor agonists, prior administration of zinc protoporphyrin IX, an inhibitor of heme oxygenase activity, significantly attenuated the cardiovascular effects of APDC and l-AP4, and failed to attenuate the cardiovascular responses of DHPG. These results indicated interactions between carbon monoxide and group II and III metabotropic glutamate receptors in central cardiovascular regulation.