Prostacyclin and Thromboxane Production by Irradiated Rat Lung

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.