Bed nucleus of the stria terminalis N-methyl-D-aspartate receptors and nitric oxide modulate the baroreflex cardiac component in unanesthetized rats.
The bed nucleus of the stria terminalis (BST) plays a tonic role modulating the baroreflex bradycardiac response. In the present study, we verified whether local BST glutamatergic receptors and nitric oxide (NO) system modulate baroreflex bradycardiac responses. Bilateral BST- N-methyl-D-aspartate (NMDA) receptor inhibition by treatment with the selective NMDA receptor antagonist LY235959 increased bradycardiac response to mean arterial pressure increases. Treatment with the selective non-NMDA antagonist NBQX did not affect reflex bradycardia. These results suggest an involvement of local NMDA receptors in the BST-related tonic inhibitory modulation of baroreflex bradycardiac response. BST treatment with the nonselective NO synthase (NOS) inhibitor L-NAME or the selective neuronal NOS (nNOS) inhibitor N(omega)-propyl-L-arginine increased bradycardiac response, indicating that NO generated by nNOS activation modulates baroreflex. The NO involvement was further reinforced by observation that BST treatment with the NO scavenger carboxy-PTIO caused an effect similar to that observed after NMDA receptor blockade or treatment with NOS inhibitors. Additionally, it was observed that LY235959 effects on baroreflex bradycardiac response were reverted by BST treatment with the NO-donor sodium nitroprusside, suggesting an NMDA receptor-NO interaction. Baroreflex bradycardiac responses observed before and after BST treatment with LY235959 or N(omega)-propyl-L-arginine were no longer different when animals were pretreated intravenously with the anticholinergic drug homatropine methyl bromide. These results indicate that parasympathetic activation accounts for the effects observed after BST pharmacological manipulation. In conclusion, our data point out that local NMDA and nNOS interaction mediates the tonic inhibitory influence of the BST on the baroreflex bradycardiac response, modulating the parasympathetic cardiac activity.
Alves
Fernando H F
FH
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Crestani
Carlos C
CC
Resstel
Leonardo B M
LB
Correa
Fernando M A
FM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012686:Septal Nuclei / Q000187:drug effects / Q000502:physiology*; D014326:Tropanes / Q000494:pharmacology
D001565:Benzoates; D018680:Cholinergic Antagonists; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D007093:Imidazoles; D007546:Isoquinolines; C109599:N(omega)-propylarginine; D020030:Nitric Oxide Donors; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D014326:Tropanes; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009599:Nitroprusside; D009569:Nitric Oxide; C056244:homatropine methylbromide; D001120:Arginine; C088643:LY 235959; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester