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Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow

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Abstract

P2X receptors are expressed on ventrolateral medulla projecting paraventricular nucleus (PVN) neurons. Here, we investigate the role of adenosine 5′-triphosphate (ATP) in modulating sympathetic nerve activity (SNA) at the level of the PVN. We used an in situ arterially perfused rat preparation to determine the effect of P2 receptor activation and the putative interaction between purinergic and glutamatergic neurotransmitter systems within the PVN on lumbar SNA (LSNA). Unilateral microinjection of ATP into the PVN induced a dose-related increase in the LSNA (1 nmol: 38 ± 6 %, 2.5 nmol: 72 ± 7 %, 5 nmol: 96 ± 13 %). This increase was significantly attenuated by blockade of P2 receptors (pyridoxalphosphate-6-azophenyl-20,40-disulphonic acid, PPADS) and glutamate receptors (kynurenic acid, KYN) or a combination of both. The increase in LSNA elicited by L-glutamate microinjection into the PVN was not affected by a previous injection of PPADS. Selective blockade of non-N-methyl-D-aspartate receptors (6-cyano-7-nitroquinoxaline-2,3-dione disodium salt, CNQX), but not N-methyl-D-aspartate receptors (NMDA) receptors (DL-2-amino-5-phosphonopentanoic acid, AP5), attenuated the ATP-induced sympathoexcitatory effects at the PVN level. Taken together, our data show that purinergic neurotransmission within the PVN is involved in the control of SNA via P2 receptor activation. Moreover, we show an interaction between P2 receptors and non-NMDA glutamate receptors in the PVN suggesting that these functional interactions might be important in the regulation of sympathetic outflow.

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Abbreviations

ATP:

Adenosine 5′-triphosphate

PPADS:

Pyridoxalphosphate-6-azophenyl-20,40-disulphonic acid

α,β-meATP:

α,β-MethyleneATP

L-glu:

L-Glutamate

KYN:

Kynurenic acid

AP5:

DL-2-Amino-5-phosphonopentanoic acid

CNQX:

6-Cyano-7-nitroquinoxaline-2,3-dione disodium salt

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Acknowledgments

This study was supported by Sao Paulo Research Foundation (FAPESP): #07/04085-0 and 10/17997-0. Ferreira-Neto HC is a recipient of a FAPESP fellowship #10/05037-1.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil

    H. C. Ferreira-Neto & V. R. Antunes

  2. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia

    S. T. Yao

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  1. H. C. Ferreira-Neto
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  3. V. R. Antunes
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Correspondence to V. R. Antunes.

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Ferreira-Neto, H.C., Yao, S.T. & Antunes, V.R. Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow. Purinergic Signalling 9, 337–349 (2013). https://doi.org/10.1007/s11302-013-9352-9

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