title: Nitric oxide modulation of glutamatergic, baroreflex, and cardiopulmonary transmission in the nucleus of the solitary tract.
abstract: The neuromodulatory effect of NO on glutamatergic transmission has been studied in several brain areas. Our previous single-cell studies suggested that NO facilitates glutamatergic transmission in the nucleus of the solitary tract (NTS). In this study, we examined the effect of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on glutamatergic and reflex transmission in the NTS. We measured mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) from Inactin-anesthetized Sprague-Dawley rats. Bilateral microinjections of L-NAME (10 nmol/100 nl) into the NTS did not cause significant changes in basal MAP, HR, or RSNA. Unilateral microinjection of (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 1 pmol/100 nl) into the NTS decreased MAP and RSNA. Fifteen minutes after L-NAME microinjections, AMPA-evoked cardiovascular changes were significantly reduced. N-methyl-D-aspartate (NMDA, 0.5 pmol/100 nl) microinjection into the NTS decreased MAP, HR, and RSNA. NMDA-evoked falls in MAP, HR, and RSNA were significantly reduced 30 min after L-NAME. To examine baroreceptor and cardiopulmonary reflex function, L-NAME was microinjected at multiple sites within the rostro-caudal extent of the NTS. Baroreflex function was tested with phenylephrine (PE, 25 microg iv) before and after L-NAME. Five minutes after L-NAME the decrease in RSNA caused by PE was significantly reduced. To examine cardiopulmonary reflex function, phenylbiguanide (PBG, 8 microg/kg) was injected into the right atrium. PBG-evoked hypotension, bradycardia, and RSNA reduction were significantly attenuated 5 min after L-NAME. Our results indicate that inhibition of NOS within the NTS attenuates baro- and cardiopulmonary reflexes, suggesting that NO plays a physiologically significant neuromodulatory role in cardiovascular regulation.
authors.affiliation: Department of Physiology, Universidade Federal de São Paulo-Escola Paulista de Medicina, Brazil.
authors.forename: Ana Carolina Rodrigues
authors.initials: AC
authors.lastname: Dias
authors.forename: Melissa
authors.initials: M
authors.lastname: Vitela
authors.forename: Eduardo
authors.initials: E
authors.lastname: Colombari
authors.forename: Steven W
authors.initials: SW
authors.lastname: Mifflin
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation; D008168:Lung / Q000294:innervation*; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001645:Biguanides; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D010656:Phenylephrine; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D019331:NG-Nitroarginine Methyl Ester; C008846:phenyl biguanide