title: Involvement of NMDA receptors in nicotine-mediated central control of hypotensive effects.
abstract: It is known that enrichment of glutamatergic transmission in the nucleus tractus solitarii (NTS) plays an important role in central cardiovascular regulation.  Our previous study demonstrated that nicotine decreased blood pressure and heart rate in the NTS probably acting via the nicotinic acetylcholine receptors (nAChRs)-Ca²⁺-calmodulin-eNOS-NO signaling pathway.  The possible relationship between glutamate and nicotine in the NTS for cardiovascular regulation is poorly understood.  This study investigated the involvement of glutamate receptors in the cardiovascular effects of nicotine in the NTS. Nicotine (a non-selective nAChRs agonist), MK801 (a non-competitive NMDA receptor antagonist), APV (a competitive NMDA receptor antagonist), or NBQX (a selective AMPA receptor antagonist) was microinjected into the NTS of anesthetized Wistar-Kyoto rats.  Microinjection of nicotine (1.5 pmol) into the NTS produced decreases in blood pressure and heart rate.  The hypotensive and bradycardic effects of nicotine were abolished by prior administration of MK801 (1 nmol) and APV (10 nmol), but was completely restored after 60 min of recovery.  In contrast, prior administration of NBQX (10 pmol) into the NTS did not alter the cardiovascular effects of nicotine.  The nitrate (served as total NO) production in response to nicotine microinjection into the NTS was suppressed by prior administration of APV. These results suggest that the hypotensive and bradycardic effects of nicotine in the NTS might be mediated through NMDA receptors, and that the nAChRs-NMDA receptor-NO pathway could be involved.
authors.affiliation: Department of Medical Education and Research, Taichung Veterans General Hospital, Taiwan, Republic of China.
authors.forename: Ling-Zong
authors.initials: LZ
authors.lastname: Hong
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Cheng
authors.forename: Wen-Han
authors.initials: WH
authors.lastname: Cheng
authors.forename: Siang-Ru
authors.initials: SR
authors.lastname: Chen
authors.forename: Ling-Lin
authors.initials: LL
authors.lastname: Wang
authors.forename: Ching-Jiunn
authors.initials: CJ
authors.lastname: Tseng
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced* / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D009538:Nicotine; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine