We investigated the hypothesis that stimulation of metabotropic excita
tory amino acid receptors in the ventrolateral medulla evokes cardiova
scular responses. Thus, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic a
cid [(1S,3R)-ACPD], a selective agonist of metabotropic excitatory ami
no acid receptors, was microinjected into the rostral or caudal ventro
lateral medulla of halothane-anesthetized Sprague-Dawley rats. Microin
jections of (1S,3R)-ACPD (100 pmol-1 nmol) into the rostral ventrolate
ral medulla produced dose-dependent increases in mean arterial pressur
e (+20+/-4 mm Hg by 100 pmol and +35+/-2 mm Hg by 1 nmol, p<0.01 versu
s artificial cerebrospinal fluid) and integrated splanchnic sympatheti
c nerve activity (+17+/-3% and +46+/-4%, respectively, p<0.01), wherea
s (1S,3R)-ACPD microinjected into the caudal ventrolateral medulla dec
reased mean arterial pressure (-28+/-2 mm Hg by 100 pmol and -48+/-6 m
m Hg by 1 nmol, p<0.01 versus artificial cerebrospinal fluid) and spla
nchnic sympathetic nerve activity (-24+/-4% and -49+/-5%, p<0.01). The
blockade of ionotropic excitatory amino acid receptors by the combine
d injection of 2-amino-7-phosphonoheptanoic acid (200 pmol) and 6,7-di
nitroquinoxaline-2,3-dione (200 pmol), which effectively blocked the r
esponses elicited by either N-methyl-D-aspartate (20 pmol) or lpha-ami
no-3-hydroxy-5-methylisoxazole-4-propionic acid (5 pmol), failed to af
fect the responses evoked by either (1S,3R)-ACPD (100 pmol) or L-gluta
mate (2 nmol) microinjected in the rostral and caudal ventrolateral me
dulla. These results suggest that metabotropic receptors are present a
nd mediate cardiovascular responses evoked by L-glutamate injections i
nto the rostral and caudal ventrolateral medulla.