METABOTROPIC GLUTAMATE RECEPTORS IN THE VENTROLATERAL MEDULLA OF RATS

We investigated the hypothesis that stimulation of metabotropic excitatory amino acid receptors in the ventrolateral medulla evokes cardiovascular responses. Thus, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], a selective agonist of metabotropic excitatory amino acid receptors, was microinjected into the rostral or caudal ventrolateral medulla of halothane-anesthetized Sprague-Dawley rats. Microinjections of (1S,3R)-ACPD (100 pmol-1 nmol) into the rostral ventrolateral medulla produced dose-dependent increases in mean arterial pressure (+20+/-4 mm Hg by 100 pmol and +35+/-2 mm Hg by 1 nmol, p<0.01 versus artificial cerebrospinal fluid) and integrated splanchnic sympathetic nerve activity (+17+/-3% and +46+/-4%, respectively, p<0.01), whereas (1S,3R)-ACPD microinjected into the caudal ventrolateral medulla decreased mean arterial pressure (-28+/-2 mm Hg by 100 pmol and -48+/-6 mm Hg by 1 nmol, p<0.01 versus artificial cerebrospinal fluid) and splanchnic sympathetic nerve activity (-24+/-4% and -49+/-5%, p<0.01). The blockade of ionotropic excitatory amino acid receptors by the combined injection of 2-amino-7-phosphonoheptanoic acid (200 pmol) and 6,7-dinitroquinoxaline-2,3-dione (200 pmol), which effectively blocked the responses elicited by either N-methyl-D-aspartate (20 pmol) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (5 pmol), failed to affect the responses evoked by either (1S,3R)-ACPD (100 pmol) or L-glutamate (2 nmol) microinjected in the rostral and caudal ventrolateral medulla. These results suggest that metabotropic receptors are present and mediate cardiovascular responses evoked by L-glutamate injections into the rostral and caudal ventrolateral medulla.