Interaction between GABA and excitatory amino acids in control of sympathetic nerve activity by the rostral ventrolateral medulla in hindlimb unloaded rats.

Abstract

Previously we have reported that pressor and sympathoexcitatory responses to blockade of γ-amino butyric acid (GABAA) receptors in the rostral ventrolateral medulla (RVLM) are enhanced in hindlimb unloaded (HU) rats, a model of cardiovascular deconditioning. Excitatory amino acids (EAAs) may play a role in the sympathoexcitation produced by removal of GABAergic tone in the RVLM. Therefore, we hypothesized that EAAs contribute to enhanced responses to GABAA blockade observed in HU rats. To test this hypothesis, rats were maintained under HU or control conditions for 14 days. Bilateral RVLM microinjections were then performed under Inactin anesthesia while recording mean arterial pressure (MAP) and lumbar sympathetic nerve activity (LSNA). The EAA antagonist kynurenate (40 mM, 90 nl) had little or no effect alone in HU or control rats but attenuated increases in MAP and LSNA produced by bicuculline (5 mM, 90nl) in both groups. However, the response to bicuculline in the presence of kynurenate was enhanced in HU versus control rats. These data suggest that although EAAs play a role in the pressor and sympathoexcitatory responses to GABAA receptor blockade in the RVLM, they do not appear to account for differences observed in control and HU rats. We speculate that differences in GABAA tone and/or non-EAA mediated transmission are responsible for enhanced responses to bicuculline in rats following a period of cardiovascular deconditioning. (Supported by HL-55306, NNA04CC626, NAG21603).