Changes in Plasma Concentrations of Prostaglandins and Plasma Angiotensin-Converting Enzyme during Bleomycin-induced Lung Fibrosis in Hamsters1–3

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Abstract
The effects of intratracheal administration of bleomycin on plasma concentrations of PGE2, PGF2α, TxB2, and 6-keto-PGF1α, total amount of lung collagen, and plasma angiotensin-converting enzyme (ACE) were studied in hamsters. The plasma concentrations of PGE2 were significantly increased from the control value of 462 pg/ml to 720, 665, and 592 pg/ml at 4, 7, and 14 days after bleomycin treatment, respectively. The plasma concentrations of PGF2α did not change at any time after treatment. The plasma concentrations of TxB2 were significantly increased from the control value of 187 pg/ml to 267, 272, 307, 257, and 253 pg/ml at 2, 4, 7, 14, and 21 days after bleomycin treatments, respectively, but decreased to 108.7 pg/ml at 28 days. Similarly, the concentrations of 6-keto-PGF1α were significantly increased from the control value of 588 pg/ml to 866, 1,186, and 963 pg/ml at 4, 14, and 21 days after bleomycin treatment, respectively, but decreased to 297.5 pg/ml at 28 days. The amount of total collagen in lung was significantly increased from the control value of 231.1 μg hydroxyproline/lung to 277.4, 481.1, 399.0, and 396.5 μg/lung at 7, 14, 21, and 28 days after bleomycin treatment, respectively. The plasma ACE was generally decreased at all time points with significant decreases occurring at 4 and 7 days after treatment. A positive correlation between the amount of total lung collagen and plasma concentrations of 6-keto-PGF1α and a negative correlation between the plasma ACE and the plasma concentrations of TxB2 were evident in hamsters treated with bleomycin. We concluded from the findings of the present study that increased circulating levels of PGE2, TxB2, and 6-keto-PGF1α are involved in bleomycin-induced lung fibrosis.