title: Nitric oxide and glutamate in the dorsal facial area regulate common carotid blood flow in the cat.
abstract: Nitric oxide (NO) or glutamate stimulation of dorsal facial area (DFA) increases blood flow in the common carotid artery (CCA), which supplies intra-and extra-cranial tissues. Nitrergic fibers and neurons as well as preganglionic cholinergic neurons are present in the DFA. We hypothesized the presence of nitrergic-glutamatergic fibers and preganglionic nitrergic-cholinergic neurons in the DFA that are involved in the regulation of CCA blood flow. In microdialysis studies, perfusion of the DFA with S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) increased the glutamate concentration in the dialysate. This effect was abolished by co-perfusion of methylene blue (a guanylyl cyclase inhibitor). Intra-DFA injection of l-arginine (an NO precursor) or glutamate increased CCA blood flow. The l-arginine-induced flow increase was reduced by prior administration 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), or glutamate diethylester (GDEE, a competitive AMPA receptor antagonist). The glutamate-induced blood flow increase was reduced by prior administration of l-NAME, 7-NI, or methylene blue. The induced increase in CCA blood flow, however, was not affected by endothelial NO synthase inhibitor. The findings indicate that NO-signal transduction within the DFA might cause glutamate release from presynaptic nitrergic-glutamatergic fibres and that the released glutamate activates NMDA/AMPA receptors on preganglionic nitrergic-cholinergic neurons in the nucleus to activate neuronal NO synthase and guanylyl cyclase in the neurons, leading to an increase in CCA blood flow. These findings may be important for developing therapeutic strategies for the diseases associated with CCA blood flow.
authors.affiliation: Neuro-Medical Scientific Center and Center for Vascular Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
authors.forename: Jon-Son
authors.initials: JS
authors.lastname: Kuo
authors.forename: Tony Jer-Fu
authors.initials: TJ
authors.lastname: Lee
authors.forename: Yung-Tsung
authors.initials: YT
authors.lastname: Chiu
authors.forename: Hsing-Tan
authors.initials: HT
authors.lastname: Li
authors.forename: Nai-Nu
authors.initials: NN
authors.lastname: Lin
authors.forename: Tzong-Toong
authors.initials: TT
authors.lastname: Tsai
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Gong
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D017536:Carotid Artery, Common / Q000294:innervation / Q000502:physiology*; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005154:Facial Nerve / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D017551:Microdialysis; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009412:Nerve Fibers / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D018698:Glutamic Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D008751:Methylene Blue; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester