title: Cardiovascular responses to L-glutamate microinjection into the hypothalamic paraventricular nucleus are mediated by a local nitric oxide-guanylate cyclase mechanism.
abstract: It has been reported that L-glutamate (L-glu) microinjection into the hypothalamic paraventricular nucleus (PVN) evokes pressor and tachycardiac responses in unanesthetized rats. In the present study the hypothesis was tested that a local nitric oxide (NO)-guanylate cyclase interaction mediates cardiovascular effects of L-glu microinjection into the PVN of rats. The cardiovascular responses evoked by 10 nmol/100 nL of L-glu microinjected into the PVN were measured before and 10 min after PVN treatment with vehicle, the selective neuronal NO-synthase (nNOS) inhibitor N(omega)-Propyl-L-arginine (N-Propyl, 0.04 nmol or 4 nmol/100 nL), the NO scavenger carboxy-PTIO (C-PTIO, 1 nmol/100 nL) or the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolol [4,3-a]quinoxalin-1-one (ODQ, 1 nmol/100 nL). In a final experiment, different doses of the NO donor sodium nitroprusside (SNP; 9, 27 or 45 nmol/100 nL) were microinjected into the PVN. Cardiovascular responses evoked by L-glu microinjection into the PVN were abolished by local pretreatment with N-Propyl in both anesthetized and unanesthetized rats. PVN treatment with either C-PTIO or ODQ also reduced L-glu cardiovascular responses. The microinjection of SNP into the PVN caused pressor and tachycardiac responses in unanesthetized rats, whereas depressor and bradycardiac responses were observed in anesthetized rats. The present results suggest that cardiovascular responses evoked by L-glu microinjection into the PVN involve a local production of NO and activation of guanylate cyclase.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Busnardo
authors.forename: Carlos C
authors.initials: CC
authors.lastname: Crestani
authors.forename: Rodrigo F
authors.initials: RF
authors.lastname: Tavares
authors.forename: Leonardo B M
authors.initials: LB
authors.lastname: Resstel
authors.forename: Fernando M A
authors.initials: FM
authors.lastname: Correa
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004347:Drug Interactions; D018698:Glutamic Acid / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008845:Microinjections / Q000379:methods; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D001565:Benzoates; D007093:Imidazoles; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011810:Quinoxalines; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009599:Nitroprusside; D009569:Nitric Oxide; D018698:Glutamic Acid; D006162:Guanylate Cyclase