title: NO differentially regulates neurotransmission to premotor cardiac vagal neurons in the nucleus ambiguus.
abstract: NO is involved in the neural control of heart rate, and NO synthase expressing neurons and terminals have been localized in the nucleus ambiguus where parasympathetic cardiac vagal preganglionic neurons are located; however, little is known about the mechanisms by which NO alters the activity of premotor cardiac vagal neurons. This study examines whether the NO donor sodium nitroprusside ([SNP] 100 micromol/L) and precursor, l-arginine (10 mmol/L), modulate excitatory and inhibitory synaptic neurotransmission to cardiac vagal preganglionic neurons. Glutamatergic, GABAergic, and glycinergic activity to cardiac vagal neurons was examined using whole-cell patch-clamp recordings in an in vitro brain slice preparation in rats. Both SNP, as well as l-arginine, increased the frequency of GABAergic neurotransmission to cardiac vagal preganglionic neurons but decreased the amplitude of GABAergic inhibitory postsynaptic currents. In contrast, both l-arginine and SNP inhibited the frequency of glutamatergic and glycinergic synaptic events in cardiac vagal preganglionic neurons. SNP and l-arginine also decreased glycinergic inhibitory postsynaptic current amplitude, and this response persisted in the presence of tetrodotoxin. Inclusion of the NO synthase inhibitor 7-nitroindazole (100 mumol/L) prevented the l-arginine-evoked responses. These results demonstrate that NO differentially regulates excitatory and inhibitory neurotransmission, facilitating GABAergic and diminishing glutamatergic and glycinergic neurotransmission to cardiac vagal neurons.
authors.affiliation: Department of Pharmacology and Physiology, George Washington University, 2300 Eye St, NW, Washington, DC 20037, USA.
authors.forename: Harriet
authors.initials: H
authors.lastname: Kamendi
authors.forename: Olga
authors.initials: O
authors.lastname: Dergacheva
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Zheng-Gui
authors.initials: ZG
authors.lastname: Huang
authors.forename: Evguenia
authors.initials: E
authors.lastname: Bouairi
authors.forename: Christopher
authors.initials: C
authors.lastname: Gorini
authors.forename: David
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001339:Autonomic Fibers, Preganglionic; D002491:Central Nervous System Agents / Q000494:pharmacology*; D006321:Heart / Q000294:innervation; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects; D018009:Receptors, Glycine / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
chemical_list: D002491:Central Nervous System Agents; D020030:Nitric Oxide Donors; D018079:Receptors, GABA; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; C069474:glutamine receptor; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine