Blockade of excitatory amino acid receptors in the ventrolateral medulla does not abolish the cardiovascular actions of l-glutamate

Injection of l-glutamate into the caudal ventrolateral medulla reduces arterial pressure while injection of l-glutamate into the rostral ventrolateral medulla increases arterial pressure. The present experiments were undertaken to determine whether blockade of excitatory amino acid receptor subtypes in the ventrolateral medulla affects the excitatory action of l-glutamate. In the rabbit and rat caudal ventrolateral medulla, injection of either dl-2-amino-5-phosphonovaleric acid (APV), an N-methyl- d-aspartic acid (NMDA) antagonist, or 6,7-dinitroquinoxaline-2,3-dione (DNQX), an α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist, increased arterial pressure. Conversely, in the rostral ventrolateral medulla these agents decreased arterial pressure. In the rabbit caudal ventrolateral medulla, injection of APV totally blocked the depressor response to NMDA, and injection of DNQX totally blocked the depressor response to either kainic acid or AMPA. Injection of both APV and DNQX abolished the effects of NMDA, kainic acid and AMPA. However caudal ventrolateral medulla injection of either APV or DNQX, or combined injection of both antagonists, did not affect the relationship between the dose of l-glutamate and the fall in arterial pressure. Similarly, in the rat, combined excitatory amino acid receptor blockade failed to reduce the depressor effect of injected l-glutamate to the caudal ventrolateral medulla. The pressor effect of l-glutamate in the rabbit rostral ventrolateral medulla, when expressed as percentage of baseline level, was unchanged by combined excitatory amino acid receptor blockade. Our results provide evidence that both NMDA and non-NMDA receptors in the caudal ventrolateral medulla and the rostral ventrolateral medulla are tonically activated. If l-glutamate is the endogenous ligand in either the caudal ventrolateral medulla or the rostral ventrolateral medulla, its action must at least partially be via a non-NMDA, non-AMPA receptor.