L-arginine (an NO precursor) or glutamate stimulation of the dorsal facial area (DFA) in the medulla increases ipsilateral common carotid arterial (CCA) blood flow. Nitrergic and glutamatergic fibers as well as nitrergic neurons are demonstrated in the DFA. Whether nitrergic and glutamatergic interactions in the DFA might regulate CCA blood flow was un-known. In microdialysis-HPLC study, perfusion in the DFA of S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, increased glutamate concentration in the DFA; Co-perfusion of methylene blue (guanylate cyclase inhibitor) with SNAP abolished SNAP-induced glutamate increase. Intra-DFA microinjection of L-arginine or L-glutamate dose-dependently increased CCA blood flow. The L-arginine-induced increase in CCA blood flow was dose-dependently blocked by pretreatment of NG-nitro-arginine methyl ester (L-NAME, a non-specific NO synthase inhibitor), 7-nitroindazole (7-NI, a relatively selective neuronal NO synthase inhibitor), D-2-amino-5-phosphonopentanoate (D-AP5, a competitive NMDA receptor antagonist), and glutamate diethylester (GDEE, a competitive AMPA receptor antagonist). The L-glutamate-induced increase in CCA blood flow was dose-dependently attenuated by pretreatment of L-NAME, 7NI, and methylene blue. Findings suggest that in the DFA glutamatergic fibers may contain neuronal NO synthase for producing NO that activate cGMP to cause release of glutamate. The glutamate then activates NMDA and AMPA receptors on the nitrergic neurons in the DFA to increase CCA blood flow. In conclusion, nitrergic-glutamatergic fibers and nitrergic neurons containing NMDA and AMPA receptors are present in the DFA for regulation of the CCA blood flow.
