Glutamate receptors of the A5 region modulate cardiovascular responses evoked from the dorsomedial hypothalamic nucleus and perifornical area

  • M. V. López-González
  • A. Díaz-Casares
  • M. González-García
  • C. A. Peinado-Aragonés
  • M. A. Barbancho
  • M. Carrillo de Albornoz
  • M. S. Dawid-Milner
Original Article

Abstract

To assess the possible function of glutamate in the interaction between the dorsomedial hypothalamic nucleus-perifornical area (DMH-PeF) and the A5 pontine region (A5), cardiovascular and respiratory changes were studied in response to electrical stimulation of the DMH-PeF (1 ms pulses, 30–50 μA given at 100 Hz for 5 s) before and after the microinjection of kynurenic acid (non-specific glutamate receptor antagonist; 50 nl, 5 nmol), MK-801 (NMDA receptor antagonist; 50 nl, 50 nmol), CNQX (non-NMDA receptor antagonist; 50 nl, 50 nmol) or MCPG (metabotropic glutamate receptor antagonist; 50 nl, 5 nmol) within the A5 region. DMH-PeF electrical stimulation elicited a pressor (p < 0.001) and tachycardic response (p < 0.001) which was accompanied by an inspiratory facilitation characterised by an increase in respiratory rate (p < 0.001) due to a decrease in expiratory time (p < 0.01). Kynurenic acid within the A5 region decreased the tachycardia (p < 0.001) and the intensity of the blood pressure response (p < 0.001) to DMH-PeF stimulation. After the microinjection of MK-801 and CNQX into the A5 region, the magnitude of the tachycardia and the pressor response were decreased (p < 0.05 and p < 0.01; p < 0.001 and p < 0.05, respectively). After MCPG microinjection into the A5 region, a decrease in the tachycardia (p < 0.001) with no changes in the pressor response was observed during DMH-PeF stimulation. The respiratory response elicited by DMH-PeF stimulation was not changed after the microinjection of kynurenic acid, MK-801, CNQX or MCPG within the A5 region. These results suggest that A5 region glutamate receptors play a role in the cardiovascular response elicited from the DMH-PeF. The possible mechanisms involved in these interactions are discussed.

Keywords

A5 region Glutamate Dorsomedial hypothalamic nucleus Perifornical area Respiratory control Cardiovascular control Rat 

References

  1. 1.
    Abbott SB, Kanbar R, Bochorishvili G, Coates MB, Stornetta RL, Guyenet PG (2012) C1 neurons excite locus coeruleus and A5 noradrenergic neurons along with sympathetic outflow in rats. J Physiol 590:2897–2915CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Benarroch EE, Schmeichel AM, Low PA, Sandroni P, Parisi JE (2008) Loss of A5 noradrenergic neurons in multiple system atrophy. Acta Neuropathol 115(6):629–634CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bruinstroop E, Cano G, Vanderhorst VG, Cavalcante JC, Wirth J, Sena-Esteves M, Saper CB (2012) Spinal projections of the A5, A6 (locus coeruleus), and A7 noradrenergic cell groups in rats. J Comp Neurol 520:1985–2001CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Byrum CE, Stornetta R, Guyenet PG (1984) Electrophysiological properties of spinally-projecting A5 noradrenergic neurons. Brain Res 303:15–29CrossRefPubMedGoogle Scholar
  5. 5.
    Byrum CE, Guyenet PG (1987) Afferent and efferent connections of the A5 noradrenergic cell group in the rat. J Comp Neurol 261:529–542CrossRefPubMedGoogle Scholar
  6. 6.
    Dampney RAL (2015) Central mechanisms regulating coordinated cardiovascular and respiratory function during stress and arousal. Am J Physiol Regul Integr Comp Physiol 309:R429–R443CrossRefPubMedGoogle Scholar
  7. 7.
    Dampney RAL (2016) Central neural control of the cardiovascular system: current perspectives. Adv Physiol Educ 40:283–296CrossRefPubMedGoogle Scholar
  8. 8.
    Dawid-Milner MS, Lara JP, Gonzalez-Baron S, Spyer KM (2001) Respiratory effects of stimulation of cell bodies of the A5 region in the anaesthetised rat. Pflugers Arch 441:434–443CrossRefPubMedGoogle Scholar
  9. 9.
    Dawid Milner MS, Lara JP, Lopez de Miguel MP, Lopez-Gonzalez MV, Spyer KM, Gonzalez-Baron S (2003) A5 region modulation of the cardiorespiratory responses evoked from parabrachial cell bodies in the anaesthetised rat. Brain Res 982:108–118CrossRefPubMedGoogle Scholar
  10. 10.
    Diaz-Casares A, Lopez-Gonzalez MV, Peinado-Aragones CA, Gonzalez-Baron S, Dawid-Milner MS (2012) Parabrachial complex glutamate receptors modulate the cardiorespiratory response evoked from hypothalamic defense area. Auton Neurosci 169:124–134CrossRefPubMedGoogle Scholar
  11. 11.
    Diaz-Casares A, Lopez-Gonzalez MV, Dawid-Milner MS (2014) Brainstem metabotropic glutamate receptors and regulation of autonomic responses. In: Foster Olive (ed) Metabotropic glutamate receptors, 1st edn. Nova Science Publisher, New York, pp 1–22Google Scholar
  12. 12.
    Dutschmann M, Herbert H (1998) NMDA and GABAA receptors in the rat Kolliker-fuse area control cardiorespiratory responses evoked by trigeminal ethmoidal nerve stimulation. J Physiol 510:793–804CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Goodchild AK, Phillips JK, Lipski J, Pilowsky PM (2001) Differential expression of catecholamine synthetic enzymes in the caudal ventral pons. J Comp Neurol 438(4):457–467CrossRefPubMedGoogle Scholar
  14. 14.
    Guthmann A, Herbert H (1999) Expression of N-methyl-D-aspartate receptor subunits in the rat parabrachial and Kölliker-fuse nuclei and in selected pontomedullary brainstem nuclei. J Comp Neurol 415(4):501–517CrossRefPubMedGoogle Scholar
  15. 15.
    Guyenet PG, Koshiya N, Huangfu D, Verberne AJ, Riley TA (1993) Central respiratory control of A5 and A6 pontine noradrenergic neurons. Am J Phys 264:1035–1044Google Scholar
  16. 16.
    Guyenet PG (2006) The sympathetic control of blood pressure. Nat Rev Neurosci 7:335–346CrossRefPubMedGoogle Scholar
  17. 17.
    Guyenet PG, Stornetta RL, Bayliss DA (2010) Central respiratory chemoreception. J Comp Neurol 518(19):3883–3906CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Hilaire G, Viemari JC, Coulon P, Simonneau M, Bevengut M (2004) Modulation of the respiratory rhythm generator by the pontine noradrenergic A5 and A6 groups in rodents. Respir Physiol Neurobiol 143:187–197CrossRefPubMedGoogle Scholar
  19. 19.
    Hilaire G (2006) Endogenous noradrenaline affects the maturation and function of the respiratory network: possible implication for SIDS. Auton Neurosci 126-127:320–331Google Scholar
  20. 20.
    Horiuchi J, McDowall LM, Dampney RA (2006) Differential control of cardiac and sympathetic vasomotor activity from the dorsomedial hypothalamus. Clin Exp Pharmacol Physiol 33(12):1265–1268CrossRefPubMedGoogle Scholar
  21. 21.
    Huangfu DH, Koshiya N, Guyenet PG (1991) A5 noradrenergic unit activity and sympathetic nerve discharge in rats. Am J Phys 261:393–402CrossRefGoogle Scholar
  22. 22.
    Jordan D, Mifflin SW, Spyer KM (1988) Hypothalamic inhibition of neurones in the nucleus tractus solitarius of the cat is GABA mediated. J Physiol 399:389–404CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kanbar R, Depuy SD, West GH, Stornetta RL, Guyenet PG (2011) Regulation of visceral sympathetic tone by A5 noradrenergic neurons in rodents. J Physiol 589:903–917CrossRefPubMedGoogle Scholar
  24. 24.
    Koshiya N, Guyenet PG (1994) A5 noradrenergic neurons and the carotid sympathetic chemoreflex. Am J Phys 267:519–526Google Scholar
  25. 25.
    Loewy AD, Gregorie EM, McKellar S, Baker RP (1979a) Electrophysiological evidence that the A5 catecholamine cell group is a vasomotor center. Brain Res 178:196–200CrossRefPubMedGoogle Scholar
  26. 26.
    Loewy AD, McKellar S, Saper CB (1979b) Direct projections from the A5 catecholamine cell group to the intermediolateral cell column. Brain Res 174:309–314CrossRefPubMedGoogle Scholar
  27. 27.
    Loewy AD (1991) Forebrain nuclei involved in autonomic control. Prog Brain Res 87:253–268CrossRefPubMedGoogle Scholar
  28. 28.
    López-González MV, Díaz-Casares A, Peinado-Aragonés CA, Lara JP, Barbancho MA, Dawid-Milner MS (2013) Neurons of the A5 region are required for the tachycardia evoked by electrical stimulation of the hypothalamic defence area in anaesthetized rats. Exp Physiol 98(8):1279–1294CrossRefPubMedGoogle Scholar
  29. 29.
    McDowall LM, Horiuchi J, Killinger S, Dampney RA (2006) Modulation of the baroreceptor reflex by the dorsomedial hypothalamic nucleus and perifornical area. Am J Physiol Regul Integr Comp Physiol 290(4):1020–1026CrossRefGoogle Scholar
  30. 30.
    Papp RS, Palkovits M (2014) Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area-an anterograde tract-tracing study. Front Neuroanat 8(34):1–16Google Scholar
  31. 31.
    Paton JFR, Spyer KM (2013) Central nervous control of cardiovascular system. In: Mathias C, Bannister R (eds) Autonomic failure. A textbook of clinical disorders of the autonomic nervous system, 5th edn. Oxford University Press, UK, pp 35–51Google Scholar
  32. 32.
    Rosin DL, Chang DA, Guyenet PG (2006) Afferent and efferent connections of the rat retrotrapezoid nucleus. J Comp Neurol 499:64–89CrossRefPubMedGoogle Scholar
  33. 33.
    Schlenker EH, Prestbo A (2003) Elimination of the post-hypoxic frequency decline in conscious rats lesioned in pontine A5 region. Respir Physiol Neurobiol 138:179–191CrossRefPubMedGoogle Scholar
  34. 34.
    Shigemoto R, Mizuno N (2000) Metabotropic glutamate receptors immunocytochemicaland in situ hybridization analyses. Handb Chem Neuroanat 18:63–98CrossRefGoogle Scholar
  35. 35.
    Silva-Carvalho L, Dawid-Milner MS, Spyer KM (1995) The pattern of excitatory inputs to the nucleus tractus solitarii evoked on stimulation in the hypothalamic defence area in the cat. J Physiol 487(3):727–737CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Tavares I, Lima D, Coimbra A (1997) The pontine A5 noradrenergic cells which project to the spinal cord dorsal horn are reciprocally connected with the caudal ventrolateral medulla in the rat. Eur J Neurosci 9:2452–2461CrossRefPubMedGoogle Scholar
  37. 37.
    Taxini CL, Takakura AC, Gargaglioni LH, Moreira TS (2011) Control of the central chemoreflex by A5 noradrenergic neurons in rats. Neuroscience 199:177–186CrossRefPubMedGoogle Scholar
  38. 38.
    Taxini CL, Moreira TS, Takakura AC, Bícego KC, Gargaglioni LH, Zoccal DB (2017) Role of A5 noradrenergic neurons in the chemoreflex control of respiratory and sympathetic activities in unanesthetized conditions. Neuroscience 354:146–157CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Wisden W, Seeburg PH, Monyer H (2000) AMPA, kainate and NMDA ionotropic glutamate receptor expression an in situ hybridization atlas. Handb Chem Neuroanat 18:99–143CrossRefGoogle Scholar

Copyright information

© University of Navarra 2018

Authors and Affiliations

  • M. V. López-González
    • 1
    • 2
  • A. Díaz-Casares
    • 1
    • 2
  • M. González-García
    • 1
    • 2
  • C. A. Peinado-Aragonés
    • 1
  • M. A. Barbancho
    • 1
  • M. Carrillo de Albornoz
    • 1
  • M. S. Dawid-Milner
    • 1
    • 2
  1. 1.Departamento de Fisiología Humana, Histología Humana, Anatomía Patológica y Educación Física y Deportiva, Facultad de MedicinaUniversidad de MálagaMálagaSpain
  2. 2.Unidad de Neurofisiología del Sistema Nervioso Autónomo (CIMES)Universidad de MálagaMálagaSpain

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