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Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat

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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.

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Acknowledgements

Willian Seiji Korim is supported by a Macquarie Research Excellence Scholarship and a Coordenadoria de Aperfeiçoamento em Pesquisa (CAPES-DS) Scholarship. Work in the Author's laboratories is supported by the National Health and Medical Research Council of Australia (457069, 457080 and 604002), Australian Research Council (DP110102110), the Garnett Passe and Rodney Williams Memorial Foundation, Macquarie University and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; #477832/2010-5).

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Authors and Affiliations

  1. Australian School of Advanced Medicine, Macquarie University, Sydney, Australia

    Willian Seiji Korim & Paul M. Pilowsky

  2. Departamento de Fisiologia, Universidade Federal de São Paulo, Rua Botucatu, 862, 04023-062, São Paulo, SP, Brazil

    Willian Seiji Korim & Sergio L. Cravo

  3. Faculdade de Educação Física, Universidade Federal de Uberlândia, Uberlândia, Brazil

    Marcos L. Ferreira-Neto

  4. Departamento de Ciências Fisiológicas, Universidade Federal de Goiás, Goiânia, Brazil

    Gustavo R. Pedrino

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  1. Willian Seiji Korim
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  2. Marcos L. Ferreira-Neto
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  5. Sergio L. Cravo
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Correspondence to Sergio L. Cravo.

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Korim, W.S., Ferreira-Neto, M.L., Pedrino, G.R. et al. Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat. Purinergic Signalling 8, 715–728 (2012). https://doi.org/10.1007/s11302-012-9318-3

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