Skip to main content

Unilateral blockade of excitatory amino acid receptors in the nucleus tractus solitarii produces an inhibiton of baroreflexes in rats

Summary

Excitatory amino acid receptors and l-glutamate in the nucleus tractus solitarii (NTS) may be involved in the regulation of baroreceptor reflexes. To evaluate this hypothesis, we microinjected amino acid antagonists unilaterally into the rat NTS, and examined their effects on cardiovascular responses to electrical stimulation of the aortic nerve and on depressor responses to excitatory amino acid agonists microinjected into the NTS. Male Wistar rats were anesthesized with urethane, paralyzed, and artifically ventilated. Kynurenate (227 ng), an excitatory amino acid antagonist, injected ipsilaterally but not contralaterally into the NTS, markedly inhibited the depressor response to aortic nerve stimulation. l-Glutamate diethylester (GDEE, 3 μg), another excitatory amino acid antagonist, injected ipsilaterally into the NTS, also markedly inhibited both reflex depressor and bradycardic responses. MK-801 (30 ng), an N-methyl-d-aspartate (NMDA) receptor channel blocker, slightly inhibited the baroreflex responses, while Joro spider toxin JSTX-3 (17 ng), a glutamate receptor antagonist, did not affect them. Kynurenate (227 ng) and GDEE (3 μg) markedly inhibited the depressor response to the NMDA receptor agonist NMDA (0.3 ng), the quisqualate receptor agonist quisqualate (0.1 ng), the kainate receptor agonist kainate (0.1 ng), and l-glutamate (10 ng), microinjected into the NTS, while MK-801 (30 ng) reduced only the depressor response to NMDA (0.3 ng), and JSTX-3 (17 ng) reduced only the depressor response to kainate (0.1 ng). These findings provide evidence for the presence of excitatory amino acid receptors involved in mediating the aortic baroreceptor reflex in the rat NTS. In addition, these observations are consistent with the hypothesis that l-glutamate or a related excitatory amino acid may be the neurotransmitter of baroreceptor information in the NTS. It appears that both NMDA and non-NMDA receptors in the rat NTS are responsible for the mediation of baroreflexes.

This is a preview of subscription content, access via your institution.

References

  1. Ciriello (1983) Brainstem projections of aortic baroreceptor afferent fibers in the rat. Neurosci Lett 36: 37–42

    Google Scholar 

  2. Cotman CW, Iversen LL (1987) Excitatory amino acids in the brain — focus on NMDA receptors. Trends Neurosci 10: 263–265

    Google Scholar 

  3. Cottle MK (1964) Degeneration studies of primary afferents of the IXth and Xth cranial nerves in the cat. J. Comp Neurol 122: 329–345

    Google Scholar 

  4. Dale N, Roberts A (1985) Dual-component amino-acid-mediated synaptic potentials: excitatory drive for swimming in Xenopus embryos. J Physiol (Lond) 363: 35–59

    Google Scholar 

  5. Foster AC, Fagg CE (1984) Acidic amino acid binding sites in mammalian neuronal membranes: their characteristics and relationship to synaptic receptors. Brain Res Rev 7: 103–164

    Google Scholar 

  6. Furuya S, Ohmori H, Shigemoto T, Sugiyama H (1989) Intracellular calcium mobilization triggered by a glutamate receptor in rat cultured hippocampal cells. J Physiol (Lond) 414: 539–548

    Google Scholar 

  7. Guyenet PG, Filtz TM, Donaldson SR (1987) Role of excitatory amino acids in rat vagal and sympathetic baroreflexes. Brain Res 407: 272–284

    Google Scholar 

  8. Humphrey SJ, McCall RB (1984) Evidence that l-glutamic acid mediates baroreceptor function in the cat. Clin Exp Hypertens [A] 6: 1311–1329

    Google Scholar 

  9. Jackson H, Nemeth EF, Parks TN (1985) Non N-methyl-d-aspartate receptors mediating synaptic transmission in the avian cochlear nucleus: effects of kynurenic acid, dipicolinic acid and streptomycin. Neuroscience 16: 171–180

    Google Scholar 

  10. Kawai N, Niwa A, Abe T (1982) Spider venom contains specific receptor blocker of glutamineric synapses. Brain Res 247: 169–171

    Google Scholar 

  11. Kleinman LI, Radford EP (1964) Ventilation standards for small mammals. J Appl Physiol 19: 360–362

    CAS  PubMed  Google Scholar 

  12. Kubo T, Amano H (1986) Vasopressin-induced pressor responses in rats to bilateral electrolytic lesioning of the caudal portion of the nucleus tractus solitarii. Brain Res 363: 183–187

    Google Scholar 

  13. Kubo T, Kihara M (1988a) Evidence of N-methyl-d-aspartate receptor-mediated modulation of the aortic baroreceptor reflex in the rat nucleus tractus solitarii. Neurosci Lett 87: 69–74

    Google Scholar 

  14. Kubo T, Kihara M (1988b) N-Methyl-d-aspartate receptors mediate tonic vasodepressor control in the caudal ventrolateral medulla of the rat. Brain Res 451: 366–370

    Google Scholar 

  15. Kubo T, Kihara M, Misu Y (1991) Ipsilateral but not contralateral blockade of excitatory amino acid receptors in the caudal ventrolateral medulla inhibits aortic baroreceptor reflex in rats. Naunyn-Schmiedeberg's Arch Pharmacol 343: 46–51

    Google Scholar 

  16. Le Galloudec E, Merahi N, Laguzzi R (1989) Cardiovascular changes induced by the local application of glutamate-related drugs in the rat nucleus tractus solitarii. Brain Res 503: 322–325

    Google Scholar 

  17. Leone C, Gordon FJ (1989) Is l-glutamate a neurotransmitter of baroreceptor information in the nucleus of the tractus solitarius? J Pharmacol Exp Ther 250: 953–962

    Google Scholar 

  18. Miura M, Reis DJ (1969) Termination of secondary projections of carotid sinus nerve in the cat brainstem. Am J Physiol 217: 142–153

    Google Scholar 

  19. Monaghan DT, Cotman CW (1985) Distribution of N-methyl-d-aspartate-sensitive L-[3H]-glutamate-binding sites in rat brain. J Neurosci 11: 2909–2919

    Google Scholar 

  20. Nakagawa T, Shirasaki T, Tateishi N, Murase K, Akaike N (1990) Effects of antagonists on N-methyl-d-aspartate response in acutely isolated nucleus tractus solitarii neurons of the rat. Neurosci Lett 113: 169–174

    Google Scholar 

  21. Palkovits M, Zaborszky L (1977) Neuroanatomy of central cardiovascular control. Nucleus tractus solitarii: afferent and efferent neuronal connections in relation to the baroreceptor reflex arc. Prog Brain Res 47: 9–34

    Google Scholar 

  22. Perrone MH (1981) Biochemical evidence that l-glutamate is a neurotransmitter of primary vagal afferent nerve fibers. Brain Res 230: 283–293

    Google Scholar 

  23. Reis DJ, Granata AR, Perrone MH, Talman WT (1981) Evidence that glutamic acid is the neurotransmitter of baroreceptor afferents terminating in the nucleus tractus solitarius (NTS). J Auton Nerv Syst 3: 321–334

    Google Scholar 

  24. Sapru HN, Krieger AJ (1977) Carotid and aortic chemoreceptor function in the rat. J Appl Physiol 42: 344–348

    Google Scholar 

  25. Sapru HN, Gonzalez E, Krieger AJ (1981) Aortic nerve stimulation in the rat: cardiovascular and respiratory responses. Brain Res Bull 6: 393–398

    Google Scholar 

  26. Stone TW, Connick JH (1985) Quinolinic acid and other kynurenines in the central nervous system. Neuroscience 15: 597–618

    Google Scholar 

  27. Talman WT (1989) Kynurenic acid microinjected into the nucleus tractus solitarius of rat blocks the arterial baroreflex but not responses to glutamate. Neurosci Lett 102: 247–252

    Google Scholar 

  28. Talman WT, Perrone MH, Reis DJ (1980) Evidence for l-glutamate as the neurotransmitter of baroreceptor afferent nerve fibers. Science 209: 813–815

    Google Scholar 

  29. Zandberg P, Palkovits M, De Jong W (1978) Effect of various lesions in the nucleus tractus solitarii of the rat on blood pressure and heart rate, and cardiovascular reflex responses. Clin Exp Hypertens [A] 1: 355–379

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to T. Kubo.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kubo, T., Kihara, M. Unilateral blockade of excitatory amino acid receptors in the nucleus tractus solitarii produces an inhibiton of baroreflexes in rats. Naunyn-Schmiedeberg's Arch Pharmacol 343, 317–322 (1991). https://doi.org/10.1007/BF00251133

Download citation

Key words

  • Aortic baroreceptor reflex
  • Excitatory amino acid receptor
  • Nucleus tractus solitarii
  • Kynurenate
  • MK-801