Skip to main content

Excitatory and Inhibitory Influences on the Ventilatory Augmentation Caused by Hypoxia

  • Chapter
Response and Adaptation to Hypoxia

Part of the book series: Clinical Physiology Series ((CLINPHY))

Abstract

Maintenance of an adequate supply of O2 to tissues depends on a complex pattern of circulatory and ventilatory adjustments that are triggered by environmental perturbations, alterations in arterial O2 levels, and changes in metabolic rate (16, 17, 66). Ventilatory responses to hypoxia are mediated by discrete neural pathways involving peripheral chemoreceptors, primary afferents, and central neurons (16, 17, 66). Hypoxia increases ventilation entirely by its effects on the peripheral chemoreceptors, mainly the carotid body (17, 18, 51, 63, 66). The characteristics of the response, however, depend on complex interactions at multiple levels of the neuraxis, including the primary afferent neurons and bulbopontine pathways through which the carotid body signals are processed and transduced to ventilation. Neurons in the nucleus of the tractus solitarius and near the ventrolateral surface of the medulla, for example, particularly in the nucleus paragigantocellularis lateralis, play a pivotal role in amplifying respiratory responses to hypercapnia and hypoxia (8, 38, 50, 62). Moreover, hypoxia can affect breathing by direct actions on the brain, including alterations in cerebral blood flow, stimulation or depression of diencephalic and cortical neurons, and possibly changes in cerebral metabolism (16–18, 54, 66).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Armstrong, D. M., V. M. Pickel, T. H. Joh, D. J. Reis, and R. J. Miller. Immunocytochemical localization of catecholamine synthesizing enzymes and neuropeptides in area prostrema and medial nucleus tractus solitarius of rat brain. J. Comp. Neurol. 196: 505–517, 1981.

    Article  PubMed  CAS  Google Scholar 

  2. Armstrong, D. M., C. A. Ross, V. M. Pickel, T. H. Jot’, and D. J. Reis. Distribution of dopamine-, noradrenaline-, and adrenaline-containing cell bodies in the rat medulla oblongata: demonstrated by the immunocytochemical localization of catecholamine biosynthetic enzymes. J. Comp. Neurol. 212: 173–187, 1982.

    Article  PubMed  CAS  Google Scholar 

  3. Berger, A. J. Distribution of carotid sinus nerve afferent fibers to solitary tract nuclei of the cat using transganglionic transport of horseradish peroxidase. Neurosci. Lett. 14: 153–158, 1979.

    Article  PubMed  CAS  Google Scholar 

  4. Bolme, P., K. Fuxe, T. Hokfelt, and M. Goldstein. Studies on the role of dopamine in cardiovascular and respiratory control: central vs. peripheral mechanisms. Adv. Biochem. Psychopharmacol. 1 6: 281–290, 1977.

    Google Scholar 

  5. Budzinska, K., C. Von Euler, F. F. KAo, T. Pantaleo, and Y. Yamamoto. Effects of graded cold block in rostral areas of medulla. Acta Physiol. Scand. 124: 329–340, 1985.

    Article  PubMed  CAS  Google Scholar 

  6. Bureau, M. A., J. Lamarche, P. Foulon, and P. Dalle. The ventilatory response to hypoxia in the newborn lamb after carotid body denervation. Respir. Physiol. 60:109–119, 1985.

    Google Scholar 

  7. Carter, D. A., and S. L. Lightman. Cardio-respiratory actions of substance P, Trh and 5–HT in the nucleus tractus solitarius of rats: evidence for functional interactions of neuropeptides and amine neurotransmitters. Neuropeptides 6: 425–436, 1985.

    Article  PubMed  CAS  Google Scholar 

  8. Cherniack, N. S., C. Von Euler, I. Homma, And F. F. KAo. Graded changes in central chemoreceptor input by local temperature changes on the ventral surface of the medulla. J. Physiol. (London) 287: 191–211, 1979.

    CAS  Google Scholar 

  9. Cuello, A. C., and I. Kanazawa. The distribution of substance P immunoreactive fibers in the rat central nervous system. J. Comp. Neurol. 178: 129–156, 1978.

    Article  PubMed  CAS  Google Scholar 

  10. Cuello, A. C., And D. S. Mcqueen. Substance P: a carotid body peptide. Neurosci. Lett. 17: 215–219, 1980.

    Article  PubMed  CAS  Google Scholar 

  11. Dahlstrom, A., and K. Fuxe. Evidence for the existence of monamine neurons in the central nervous system. II. Experimentally induced changes in the amine levels of bulbospinal neuron systems. Acta Physiol. Scand. 247: 1–36, 1965.

    Google Scholar 

  12. Davies, R. O., and M. W. Edwards, JR. Distribution of carotid body chemoreceptor afferents in the medulla of the cat. Brain Res. 64: 451–454, 1973.

    Article  PubMed  CAS  Google Scholar 

  13. Davies, R. O., and M. Kalia. Carotid sinus nerve projections to the brain stem in the cat. Brain Res. Bull. 6: 531–541, 1981.

    Article  PubMed  CAS  Google Scholar 

  14. Donoghue, S., R. B. Felder, D. Jordan, and K. M. Spyer. The central projections of carotid baroreceptors and chemoreceptors in the cat: a neurophysiological study. J. Physiol. (London) 347: 397–409, 1984.

    CAS  Google Scholar 

  15. Euler, C. Von. Brain stem mechanisms for generation and control of breathing pattern. In: Handbook of Physiology, Section 3, Vol. II, ed. N. S. Cherniack and J. G. Widdicombe. Bethesda, MD: American Physiological Society, 1986, pp. 1–68.

    Google Scholar 

  16. Eyzaguirre, C., and P. Zapata. Perspectives in carotid body research. J. Appl. Physiol. 57: 931–957, 1984.

    PubMed  CAS  Google Scholar 

  17. Fidone, S. J., and C. Gonzalez Initiation and control of chemoreceptor activity in the carotid body. In: Handbook of Physiology, Section 3, Vol. II, ed. N. S. Cherniack and J. G. Widdicombe. Bethesda, MD: American Physiological Society, 1986, pp. 247–312.

    Google Scholar 

  18. Fitzgerald, R. S., and S. Lahiri. Reflex responses to chemoreceptor stimulation. In: Handbook of Physiology, Section 3, Vol. II, ed. N. S. Cherniack and J. G. Widdicombe. Bethesda, MD: American Physiological Society, 1986, pp. 313–362.

    Google Scholar 

  19. Folgering, H., J. Ponte, and T. Sadig. Adrenergic mechanisms and chemoreception in the carotid body of the cat and rabbit. J. Physiol. (London) 325: 1–21, 1982.

    CAS  Google Scholar 

  20. Gillis, R. A., C. J. Helke, B. L. Hamilton, W. P. Norman, and D. M. Jacobowitz. Evidence that substance P is a neurotransmitter of baro-and chemoreceptor afferents in nucleus tractus solitarius. Brain Res. 181: 476–481, 1980.

    Article  PubMed  CAS  Google Scholar 

  21. Helke, C. J., T. L. O’Donoghue, and D. M. Jacobowitz. Substance P as a baro-and chemoreceptor afferent neurotransmitter: immunocytochemical and neurochemical evidence in the rat. Peptides 1: 109, 1980.

    Article  Google Scholar 

  22. Helke, C. J., D. M. Jacobowitz, And N. B. Thoa. Capsaicin and potassium evoked substance P release from the nucleus tractus solitarius and spinal trigeminal nucleus in vitro. Life Sci. 29: 1779–1785, 1981.

    Article  PubMed  CAS  Google Scholar 

  23. Helke, C. J., J. J. Neil, V. J. Massari, and A. D. Loewy. Substance P neurons project from the ventral medulla to the intermediolateral cell column and ventral horn in the rat. Brain Res. 243: 147–152, 1982.

    Article  PubMed  CAS  Google Scholar 

  24. Hokfelt, T., J. Kellerth, A. Ljungdahl, G. Nilsson, A. Nygards, And B. Pernow. Immunohistochemical localization of substance P in the central and peripheral nervous systems. In: Neuroregulators and Psychiatric Disorders, ed. E. Usdin, D. A. Hamburg, and J. D. Barchos. New York: Oxford University Press, 1977, pp. 299–311.

    Google Scholar 

  25. Jacobowitz, D. M., and C. J. Helke. Localization of substance P immunoreactive nerves in the carotid body. Brain Res. Bull. 5: 195–197, 1980.

    Article  PubMed  CAS  Google Scholar 

  26. Jordan, D. And K. M. Spyer. Studies on the termination of sinus nerve afferents. Pflugers Arch. 369: 65–73, 1977.

    Article  PubMed  CAS  Google Scholar 

  27. Kalia, M., and M. Mesulam. Brainstem projections of the sensory and motor components of the vagus complex in the cat. II. Laryngeal, tracheobronchial, pulmonary, cardiac and GI branches. J. Comp. Neurol. 193: 467–508, 1980.

    Article  PubMed  CAS  Google Scholar 

  28. Kalia, M., K. Fuxe, and M. Goldstein. Rat medulla oblongata. II. Dopaminergic, nonadrenergic (Al and A2) and adrenergic neurons, nerve fibers, and presumptive terminal processes. J. Comp. Neurol. 233: 308–332, 1985.

    Article  PubMed  CAS  Google Scholar 

  29. Katz, D. M., and H. J. Karten. Substance P in the vagal sensory ganglia: localization in cell bodies and pericellular arborizations. J. Comp. Neurol. 193: 549–564, 1980.

    Article  PubMed  CAS  Google Scholar 

  30. Katz, D. M., K. A. Markey, J. E. Adler, and I. B. Black. Target regulation of adult sensory neurotransmitter plasticity. Soc. Neurosci. (Abstr) 9: 305, 1983.

    Google Scholar 

  31. Katz, D. M., K. A. Markey, M. Goldstein, and I. B. Black. Expression of catecholaminergic characteristics by primary sensory neurons in the normal adult rat in vivo. Proc. Natl. Acad. Sci. (Usa) 80: 3526–3530, 1983.

    Article  CAS  Google Scholar 

  32. Katz, D. M., J. E. Adler, and I. B. Black. Peptide regulation of catecholaminergic transmitter metabolism in adult primary sensory neurons in vitro. Soc. Neurosci. (Abstr) 11: 668, 1985.

    Google Scholar 

  33. Katz, D. M., and I. B. Black. Expression and regulation of catecholaminergic traits in primary sensory neurons: relationship to target innervation in vivo. J. Neurosci. 6: 983–989, 1986.

    PubMed  CAS  Google Scholar 

  34. Katz, D. M., J. E. Adler, And I. B. Black. Expression and regulation of tyrosine hydroxylase in adult sensory neurons in culture: effects of elevated potassium and nerve growth factor. Brain Res. 385: 68–73, 1986.

    Article  PubMed  CAS  Google Scholar 

  35. King, G. W. Topology of ascending brainstem projections to nucleus parabrachialis of the cat. J. Comp. Neurol. 191: 615–638, 1980.

    Article  PubMed  CAS  Google Scholar 

  36. Landis, S. G., N. R. Prabhakar, J. Mitra, and N. S. Cherniack. Localization of substance P and Cgrp immunoreactivity in the cat carotid body. Fed. Proc. 46: 824, 1987.

    Google Scholar 

  37. Liebstein, A. G., R. Dermietzel, I. M. Willenberg, and J. Dauschert. Mapping Of different neuropeptides in the lower brainstem of the rat: with special reference to the ventral surface. J. Auton. Nerv. Syst. 14: 299–313, 1985.

    Article  Google Scholar 

  38. Loeshcke, H. H. Central chemosensitivity and the reaction theory. J. Physiol. (London) 332:1–24, 1982.

    Google Scholar 

  39. Loewy, A. D., and H. Burton. Nuclei of the solitary tract: efferent projections to the lower brain stem and spinal cord of the cat. J. Comp. Neurol. 1 81: 421–450, 1978.

    Article  Google Scholar 

  40. Loewy, A. D., J. H. Wallach, And S. Mckellar. Efferent connections of the ventral medulla oblongata in the rat. Brain Res. 3: 63–80, 1981.

    Article  Google Scholar 

  41. Lundberg, J. M., T. Hokfelt, H. Fahrenkrug, G. Nilsson, and L. Terenius. Peptides in the cat carotid body (glomus caroticum): Vip-, enkephalin-, and substance P-like im-munoreactivity. Acta Physiol. Scand. 107: 279–281, 1979.

    Article  PubMed  CAS  Google Scholar 

  42. Moracic, V, G. K. Kumar, E. C. Deal, N. S. Cherniack, and M. A. Haxhiu. Neutral endopeptidase (Nep) is present in the ventrolateral medulla (Vlm). Fed. Proc. (Abst)1027: A403, 1989.

    Google Scholar 

  43. Maley, B., and R. Elde. Immunohistochemical localization of putative neurotransmitters within the feline nucleus tractus solitarii. Neuroscience 7: 2469–2490, 1982.

    Article  PubMed  CAS  Google Scholar 

  44. Matsas, R., A. J. Kenny, and A. J. Turner. The metabolism of neuropeptides: the hydrolysis of peptides including enkephalins, tachykinins and their analogues by endopeptidase 24.11. Biochem. J. 223: 443–440, 1984.

    Google Scholar 

  45. Mcallen, R. M., J. J. Neil, and A. D. Loewy. Effects of kainic acid applied to the ventral surface of the medulla oblongata on vasomotor tone, the baroreceptor reflex and hypothalamic autonomic response. Brain Res. 238: 65–76, 1982.

    Article  PubMed  CAS  Google Scholar 

  46. Mcallen, R. M. Location of neurons with cardiovascular and respiratory function at the ventral surface of the cat’s medulla. Neuroscience 18: 43–49, 1986.

    Article  PubMed  CAS  Google Scholar 

  47. Mcdonald, D. M., and R. A. Mitchell. The innervation of the glomus cells, ganglion cells and blood vessels in the rat carotid body: a quantitative ultrastructural analysis. J. Neurocytol. 4: 177–230, 1975.

    Article  Google Scholar 

  48. Mcqueen, D. S. Effects of substance P on carotid chemoreceptor activity in the cat. J. Physiol. (London) 302: 31–47, 1980.

    CAS  Google Scholar 

  49. Millhorn, D. E. Neural respiratory and circulatory interaction during chemoreceptor stimulation and cooling of ventral medulla in cat. J. Physiol. (London) 370: 217–231, 1986.

    CAS  Google Scholar 

  50. Millhorn, D. E., and F. Eldridge. Role of ventrolateral medulla in regulation of respiratory and cardiovascular system. J. Appl. Physiol. 61: 1249–1263, 1986.

    PubMed  CAS  Google Scholar 

  51. Mitra, J., N. R. Prabhakar, T. Pantaleo, M. Runold, E. Van Lunteren, C. Von Euler, and N. S. Cherniack. Do structures in the region of nucleus paragigantocellularis (nPG) integrate and mediate ventilatory drive inputs? Soc. Neurosci. (Abstr) 12: 304, 1986.

    Google Scholar 

  52. Miura, M., And D. J. Reis. Termination and secondary projections of carotid sinus nerve in the cat brain stem. Am. J. Physiol. 217: 142–153, 1969.

    Google Scholar 

  53. Mulligan, E., S. Lahiri, A. Mokashi, S. Matsumoto, and K. H. Mcgregor. Adrenergic mechanisms in oxygen chemoreception in the cat aortic body. Respir. Physiol. 63: 375382, 1986.

    Google Scholar 

  54. Neubauer, J. A., T. V. Santiago, M. A. Posner, and N. H. Edelman. Ventral medullary pH and ventilatory responses to hyperperfusion and hypoxia. J. Appl. Physiol. 58: 1659 1668, 1985.

    Google Scholar 

  55. Panneton, W. M., And A. D. Loewy. Projections of the carotid sinus nerve to the nucleus of the solitary tract in the cat. Brain Res. 191:239–244, 1980.

    Google Scholar 

  56. Prabhakar, N. R., M. Runold, Y. Yamamoto, H. Lagercrantz, and C. Von Euler. Effect of substance P antagonist on the hypoxia-induced and carotid chemoreceptor activity. Acta Physiol. Scand. 121: 301–303, 1984.

    Article  PubMed  CAS  Google Scholar 

  57. Prabhakar, N. R., J. Mitra, E. M. Adams, and N. S. Cherniack. Role of substance Pin the hypercapnic excitation of carotid chemoreceptors. Fed. Proc. 45: 160, 1986.

    Google Scholar 

  58. Prabhakar, N. R., J. Mitra, And N. S. Cherniack. Role of substance P in hypercapnic excitation of carotid chemoreceptors. J. Appl. Physiol. 63: 2418–2425, 1987.

    CAS  Google Scholar 

  59. Prabhakar, N. R., J. Mitra, H. Lagercrantz, C. Von Euler, and N. S. Cherniack. Substance P and hypoxic excitation of the carotid body. In: Substance P and Neurokinins, ed. J. L. Henry, R. Couture, A. C. Cuello, G. Pelletier, R. Quirion, and D. Regoli. New York: Springer-Verlag, 1988, pp. 263–265.

    Google Scholar 

  60. Prabhakar, N. R., S. C. Landis, G. K. Kumar, D. Millikin-Kilpatrick, N.S. Cherniack, and S. E. Leeman. Substance P and neurokinin A in the cat carotid body: localization, exogeneous effects and changes in content in response to arterial Po,. Brain Res. 481:205214, 1989.

    Google Scholar 

  61. Ricardo, J. A., and E. T. Koh. Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat. Brain Res. 153: 1–26, 1978.

    Article  PubMed  CAS  Google Scholar 

  62. Schlaefke, M. E. Central chemosensitivity: a respiratory drive. Reu. Physiol. Biochem. Pharmacol. 90: 171–244, 1981.

    Article  CAS  Google Scholar 

  63. Schramm, C. M., and M. Grunstein. Respiratory influence of peripheral chemoreceptor stimulation in maturing rabbits. J. Appl. Physiol. 63:1671–1680, 1987.

    Google Scholar 

  64. Taber, E. The cytoarchitecture of the brain stem of the cat. I. Brain stem nuclei of the cat. J. Comp. Neurol. 116: 27–70, 1961.

    Article  PubMed  CAS  Google Scholar 

  65. Van Lunteren, E., J. Mitra, N. R. Prabhakar, M. A. Haxhiu, and N. S. Cherniack. Ventral

    Google Scholar 

  66. medullary surface inputs to cervical sympathetic respiratory oscillations. Am. J. Physiol. 252 (Reg. Integ. Comp. Physiol. 21): R1032–1038, 1987.

    Google Scholar 

  67. Weil, J. V. Ventilatory control at high altitude. In: Handbook of Physiology, Section 3, Vol. II, ed. N. S. Cherniack and J. G. Widdicombe. Bethesda, MD: American Physiological Society, 1986, pp. 703–727.

    Google Scholar 

  68. Yamamoto, Y., and H. Lagercrantz. Some effects of substance P on central respiratory control in rabbit pups. Acta Physiol. Scand. 124: 449–455, 1985.

    Article  PubMed  CAS  Google Scholar 

  69. Yamamoto, Y., and H. Lagercrantz. Substance P: a putative mediator of the hypoxic drive. In: Neurobiology of the Control of Breathing, ed. C. von Euler and H. Lagercrantz. New York: Raven, 1986, pp. 97–100.

    Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1991 American Physiological Society

About this chapter

Cite this chapter

Cherniack, N.S., Prabhakar, N., Haxhiu, M.A., Runold, M. (1991). Excitatory and Inhibitory Influences on the Ventilatory Augmentation Caused by Hypoxia. In: Lahiri, S., Cherniack, N.S., Fitzgerald, R.S. (eds) Response and Adaptation to Hypoxia. Clinical Physiology Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7574-3_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-7574-3_10

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-7574-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics