Interaction between glutamatergic and nitrergic mechanisms mediating cardiovascular responses to l-glutamate injection in the diagonal band of Broca in anesthetized rats

In a previous study, we reported depressor and bradycardiac responses after l-glutamate (l-glu) microinjection into the diagonal band of Broca (dbB) in anesthetized rats. Here, we report the glutamatergic-receptor subtype mediating the cardiovascular effects evoked by l-glu injection into the dbB and the involvement of local nitric oxide (NO) mechanisms as well as peripheral effectors. Microinjections of 100 nL of l-glu (1, 27, 81, 130 or 200 nmol) into the dbB of urethane-anesthetized rats caused short-lasting depressor and bradycardiac responses. Responses were dose-related, with an ED50 of approximately 81 nmol. This dose was used in later experiments. The cardiovascular responses to l-glu in the dbB were abolished by local pretreatment (100 nL) with the selective N-methyl-d-aspartic acid (NMDA) receptor antagonist LY235959 (4 nmol) but were not affected by pretreatment with the selective non-NMDA receptor antagonist NBQX (4 nmol). Responses to l-glu in the dbB were blocked by local pretreatment with the selective neuronal NO-synthase (nNOS) inhibitor Nω-propyl-l-arginine (NPLA, 0.04 nmol); the NO scavenger carboxy-PTIO (C-PTIO, 1 nmol) or the guanylate cyclase inhibitor ODQ (1 nmol). These results suggest that the microinjection of l-glu into the dbB of urethane-anesthetized rats causes dose-related depressor and bradycardiac responses through the NMDA receptor–NO-guanylate cyclase pathway.