Advertisement

Prostacyclin and Thromboxane Production by Irradiated Rat Lung

  • W. F. Ward
  • J. M. Hinz

Abstract

The production of prostacyclin (PGI2) and thromboxane (TXA2) by irradiated rat lung and the concentration of these prostanoids in the bronchoalveolar lavage (BAL) fluid were measured in rats sacrificed at 2 or 6 months after a single dose of 10-30 Gy of cobalt-60 gamma rays to the right hemithorax. Lung PGI2 and TXA2 production increased linearly with increasing radiation dose at rates of 3.1% and 4.3% per Gy, respectively, at 2 months and 21.7% and 6.1% per Gy, respectively, at 6 months. At both times, PGI2 and TXA2 production tended to plateau at doses of 25 Gy or higher. This plateau usually disappeared in the presence of exogenous arachidonic acid, suggesting that the Vmax for PGI2 production at 2 and 6 months and for TXA2 at 6 months was substrate-limited rather than enzyme-limited. At 2 months after irradiation, the modifying agents D-penicillamine (an inhibitor of collagen cross-linking) and Captopril (an angiotensin-converting enzyme inhibitor) exhibited significant dose-reduction factors of 1.3-1.8 for PGI2 production and 1.3-1.4 for TXA2 production. In the shielded left lung, PGI2 production increased slightly but significantly with increasing contralateral dose at 2 months postirradiation. The concentration of TXA2 in the BAL fluid increased linearly with increasing radiation dose at 2 months after exposure, whereas PGI2 concentration was independent of dose. At 6 months, the reverse was true. These data demonstrate that hemithorax irradiation produces a dose-dependent increase in pulmonary PGI2 and TXA2 production for at least 6 months, and suggest that BAL data may serve as an index of radiation-induced pulmonary damage.

Keywords

Radiation Injury Increase Radiation Dose Exogenous Arachidonic Acid PGI2 Production Irradiate Lung 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Law, M. P. Radiation-induced vascular injury and its relation to late effects in normal tissues. Adv. Radiat. Biol. 9: 37–73, 1981.Google Scholar
  2. 2.
    Withers, H. R., Peters, L. J., and Kogelnick, H. D. The pathobiology of late effects of irradiation. In: “Radiation Biology in Cancer Research.” R. E. Meyn and H. R. Withers, eds. Raven Press, New York, 1980, pp. 439–448.Google Scholar
  3. 3.
    Hirose, T. Prostacyclin as a modulator of acute lung injury. In: “The Pulmonary Circulation and Acute Lung Injury.” S. I. Said, ed. Futura Publishing, Mt. Kisco, New York, 1985, pp. 455–467.Google Scholar
  4. 4.
    Demling, R. H. Role of prostaglandins in acute pulmonary microvascular injury. Ann. N.Y. Acad. Sci. 384: 517–534, 1982.PubMedCrossRefGoogle Scholar
  5. 5.
    Saldeen, P., and Saldeen, T. 6-Keto-prostaglandin F/thromboxane B2 ratio in vascular and lung tissue. Thromb. Res, 30: 643–650, 1983.PubMedCrossRefGoogle Scholar
  6. 6.
    Steel, L. K., and Catravas, G. N. Radiation-induced changes in production of prostaglandins F, E, and thromboxane B2 in guinea pig parenchymal lung tissues. Int. J. Radiat. Biol. 42: 517–530, 1982.CrossRefGoogle Scholar
  7. 7.
    Ts’ao, C., Ward, W. F., and Port, C. D. Radiation injury in rat lung. I. Prostacyclin (PGI2) production, arterial perfusion, and ultrastructure. Radiat. Res. 96: 284–293, 1983.Google Scholar
  8. 8.
    Ward, W. F., Molteni, A., Ts’ao, C., and Solliday, N. H. Radiation injury in rat lung. IV. Modification by D-penicillamine. Radiat. Res. 98: 397–406, 1984.Google Scholar
  9. 9.
    Heinz, T. R., Schneidkraut, M. J., Kot, P. A., Ramwell, P. W., and Rose, J. C. Radiation-induced alterations in cyclooxygenase product synthesis by isolated perfused rat lungs. Prog. Biochem. Pharmacol. 20: 74–83, 1985.PubMedGoogle Scholar
  10. 10.
    Ward, W. F., Molteni, A., Ts’ao, C., and Solliday, C., D. Bleomycin-induced pulmonary endothelial dysfunction in mice: Failure of indomethacin to ameliorate damage. Fed. Proc. 44: 1263, 1985.Google Scholar
  11. 11.
    Molteni, A., Ward, W. F., Ts’ao, C., Port, C. D., and Solliday, N. H. Monocrotaline-induced pulmonary endothelial dysfunction in rats. Proc. Soc. Exp. Biol. Med. 176: 88–94, 1984.PubMedGoogle Scholar
  12. 12.
    Ward, W. F., Shih-Hoellwarth, A., and Tuttle, R. D. Collagen accumulation in irradiated rat lung: Modification by D-penicillamine. Radiology 146: 533–537, 1983.PubMedGoogle Scholar
  13. 13.
    Ward, W. F., Shih-Hoellwarth, A., Port, C. D., and Kim, Y. T. Modification of radiation-induced pulmonary fibrosis in rats. Radiology 131: 751–758, 1979.PubMedGoogle Scholar
  14. 14.
    Molteni, A., Ward, W. F., Ts’ao, C., Solliday, N. H., and Dunne, M. Monocrotaline-induced pulmonary fibrosis in rats: Amelioration by Captopril and penicillamine. Proc Soc Exp. Biol. Med. 180: 112–120, 1985.PubMedGoogle Scholar
  15. 15.
    Zar, J. H. Biostatistical Analysis. Prentice-Hall, Englewood Cliffs, NJ, 1974, pp. 121–181.Google Scholar
  16. 16.
    Port, C. D., and Ward, W. F. The ultrastructure of radiation injury in rat lung: Modification by D-penicillamine. Radiat. Res. 92: 61–82, 1982.PubMedCrossRefGoogle Scholar
  17. 17.
    Ts’ao, C., and Ward, W. F. Plasminogen activator activity in lung and alveolar macrophages of rats exposed to graded single doses of gamma rays to the right hemithorax. Radiat. Res. 103: 393–402, 1985.CrossRefGoogle Scholar
  18. 18.
    Ward, W. F. Radiation-induced pulmonary arterial perfusion defects: Modification by D-penicillamine. Radiology 139: 201–204, 1981.PubMedGoogle Scholar
  19. 19.
    Ward, W. F., Molteni, A., Solliday, N. H., and Jones, G. E. The relationship between endothelial dysfunction and collagen accumulation in irradiated rat lung. Int. J. Radiat. Oncol. Biol. Phys. 11: 1985–1990, 1985.PubMedCrossRefGoogle Scholar
  20. 20.
    Donlon, M., Steel, L., Helgeson, E. A., Shipp, A., and Catravas, G. N. Radiation-induced alterations in prostaglandin excretion in the rat. Life Sci. 32: 2631–2639, 1983.PubMedCrossRefGoogle Scholar
  21. 21.
    Schneidkraut, M. J., Kot, P. A., Ramwell, P. W., and Rose, J. C. Urinary prostacyclin and thromboxane levels after whole-body gamma irradiation in the rat. Adv. Prostaglandin Thromboxane Leukotriene Res. 12: 107–111, 1983.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • W. F. Ward
    • 1
  • J. M. Hinz
    • 1
  1. 1.Department of RadiologyNorthwestern University Medical SchoolChicagoUSA

Personalised recommendations