Interaction between glutamatergic and nitrergic mechanisms mediating cardiovascular responses to L-glutamate injection in the diagonal band of Broca in anesthetized rats.
In a previous study, we reported depressor and bradycardiac responses after L-glutamate (L-glu) microinjection into the diagonal band of Broca (dbB) in anesthetized rats. Here, we report the glutamatergic-receptor subtype mediating the cardiovascular effects evoked by L-glu injection into the dbB and the involvement of local nitric oxide (NO) mechanisms as well as peripheral effectors. Microinjections of 100 nL of L-glu (1, 27, 81, 130 or 200 nmol) into the dbB of urethane-anesthetized rats caused short-lasting depressor and bradycardiac responses. Responses were dose-related, with an ED(50) of approximately 81 nmol. This dose was used in later experiments. The cardiovascular responses to L-glu in the dbB were abolished by local pretreatment (100 nL) with the selective N-methyl-D-aspartic acid (NMDA) receptor antagonist LY235959 (4 nmol) but were not affected by pretreatment with the selective non-NMDA receptor antagonist NBQX (4 nmol). Responses to L-glu in the dbB were blocked by local pretreatment with the selective neuronal NO-synthase (nNOS) inhibitor N(omega)-propyl-L-arginine (NPLA, 0.04 nmol); the NO scavenger carboxy-PTIO (C-PTIO, 1 nmol) or the guanylate cyclase inhibitor ODQ (1 nmol). These results suggest that the microinjection of L-glu into the dbB of urethane-anesthetized rats causes dose-related depressor and bradycardiac responses through the NMDA receptor-NO-guanylate cyclase pathway.
Tavares
Rodrigo Fiacadori
RF
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Av. Bandeirantes, 3900, CEP: 14090-090, Brazil.
Resstel
Leonardo Barbosa Moraes
LB
Corrêa
Fernando Morgan Aguiar
FM
D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D020667:Diagonal Band of Broca / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008845:Microinjections / Q000379:methods; D026602:Nitrergic Neurons / Q000187:drug effects* / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000502:physiology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D001565:Benzoates; D007093:Imidazoles; D007546:Isoquinolines; C109599:N(omega)-propylarginine; D010069:Oxadiazoles; D011810:Quinoxalines; D017470:Receptors, Glutamate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D018698:Glutamic Acid; D001120:Arginine; C088643:LY 235959