Prostacyclin and Thromboxane Production by Irradiated Rat Lung
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.
KeywordsRadiation Injury Increase Radiation Dose Exogenous Arachidonic Acid PGI2 Production Irradiate Lung
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- 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.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.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
- 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.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
- 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
- 15.Zar, J. H. Biostatistical Analysis. Prentice-Hall, Englewood Cliffs, NJ, 1974, pp. 121–181.Google Scholar
- 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