Effect of pulmonary oedema induced by alpha-naphthylthiourea on synthesis of cyclo-oxygenase products in rat isolated lungs.

Synthesis of COP (prostaglandins; PG and thromboxanes; Tx) from exogenous and endogenous arachidonic acid (AA) was studied in isolated perfused lungs from rats treated in vivo with a single dose of alpha-naphthylthiourea (ANTU; 10mg/kg;). Lung dry:wet weight ratios showed changes characteristic of oedema between 6 and 16h after ANTU. Bioassay of COP showed that COP synthesis from exogenous AA was raised above control values in lungs from rats treated with ANTU, reaching a maximum at 16h after treatment. By radioimmunoassay, the major increase was in 6-oxo-PGF1 alpha, with lesser effects on PGE2 and PGF2 alpha levels. Synthesis of bioassayable COP from endogenous AA induced by the calcium ionophore A23187 was increased as early as 2h after ANTU treatment and remained elevated up to 70h. In lungs 28h after ANTU, 6-oxo-PGF1 alpha release was greater than in normal lungs. These results show that in this model of pulmonary oedema, the potential for COP synthesis was increased. From the time course of this effect, increased COP synthesis was probably a response to the initial damage rather than a cause of the oedema.