title: Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat.
abstract: In the nucleus tractus solitarii (NTS) of rats, blockade of extracellular ATP breakdown to adenosine reduces arterial blood pressure (AP) increases that follow stimulation of the hypothalamic defense area (HDA). The effects of ATP on NTS P2 receptors, during stimulation of the HDA, are still unclear. The aim of this study was to determine whether activation of P2 receptors in the NTS mediates cardiovascular responses to HDA stimulation. Further investigation was taken to establish if changes in hindlimb vascular conductance (HVC) elicited by electrical stimulation of the HDA, or activation of P2 receptors in the NTS, are relayed in the rostral ventrolateral medulla (RVLM); and if those responses depend on glutamate release by ATP acting on presynaptic terminals. In anesthetized and paralyzed rats, electrical stimulation of the HDA increased AP and HVC. Blockade of P2 or glutamate receptors in the NTS, with bilateral microinjections of suramin (10 mM) or kynurenate (50 mM) reduced only the evoked increase in HVC by 75 % or more. Similar results were obtained with the blockade combining both antagonists. Blockade of P2 and glutamate receptors in the RVLM also reduced the increases in HVC to stimulation of the HDA by up to 75 %. Bilateral microinjections of kynurenate in the RVLM abolished changes in AP and HVC to injections of the P2 receptor agonist α,β-methylene ATP (20 mM) into the NTS. The findings suggest that HDA-NTS-RVLM pathways in control of HVC are mediated by activation of P2 and glutamate receptors in the brainstem in alerting-defense reactions.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
authors.forename: Willian Seiji
authors.initials: WS
authors.lastname: Korim
authors.forename: Marcos L
authors.initials: ML
authors.lastname: Ferreira-Neto
authors.forename: Gustavo R
authors.initials: GR
authors.lastname: Pedrino
authors.forename: Paul M
authors.initials: PM
authors.lastname: Pilowsky
authors.forename: Sergio L
authors.initials: SL
authors.lastname: Cravo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply*; D007022:Hypotension / Q000378:metabolism; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D017470:Receptors, Glutamate; D018048:Receptors, Purinergic P2; D013498:Suramin; D000255:Adenosine Triphosphate; D007736:Kynurenic Acid