Reciprocal regulation of nitric oxide and glutamate in the nucleus tractus solitarii of rats

Abstract Nitric oxide (NO) and glutamate are both important mediators of the central cardiovascular regulation in the nucleus tractus solitarii. Our previous studies revealed that the central cardiovascular effects of NO in the nucleus tractus solitarii could be inhibited by glutamate receptor blockade. On the other hand, nitric oxide synthase (NOS) inhibitor attenuated the cardiovascular effects of glutamate. Thus, NO and glutamatergic systems appear to interact in central cardiovascular regulation. The present study examined whether NO and glutamate may affect each other's release/production in the nucleus tractus solitarii. A microdialysis probe was implanted into the nucleus tractus solitarii of male Sprague–Dawley rats, and the changes in the extracellular levels of glutamate and NO were determined by high performance liquid chromatography coupled with electrochemical detection and an NO analyzer, respectively. The results showed that NO solution elicited >10 fold increases in the extracellular level of glutamate, which returned to normal 60 min after the end of NO perfusion. The NO donor N -acetyl-penicillamine (SNAP) had an effect similar to NO solution. Furthermore, the glutamate level was reduced to 61% of basal value by perfusion with the NOS inhibitor, N G -monomethyl- l -arginine ( l -NMMA). When glutamate receptor agonist N -methyl- d -aspartic acid (NMDA) or α-amino-3-hydroxy-5-methylixoxazole-4-propionic acid (AMPA) was administered into the nucleus tractus solitarii, the extracellular NO level was increased by 70–100%, whereas glutamate receptor antagonists (MK-801 hydrogen maleate and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) did not alter the basal levels of NO. These results suggest that NO and glutamate may enhance each other's release/production in the nucleus tractus solitarii. This reciprocal regulation of NO and glutamate may be important in central cardiovascular control in the nucleus tractus solitarii.