Thromboxane and prostacyclin synthesis following whole body irradiation in rats

The effect of radiation on the mechanism and source of in vivo thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) synthesis was evaluated. Rats were irradiated with 2, 10, or 20 gray (Gy) whole-body gamma irradiation and showed an increase in urine TxB2 after either 10 or 20 Gy. Urine 6-keto-PGF1 alpha was elevated only after exposure to 20 Gy. Irradiation did not alter urine volume or osmolarity, nor was there a correlation between urine osmolarity and the urinary concentration of TxB2 r 6-keto-PGF1 alpha. Rats were pretreated with indomethacin to determine if radiation-induced alterations in urine TxB2 and 6-keto-PGF1 alpha could be suppressed. Pretreatment with indomethacin significantly decreased urine TxB2 and 6-keto-PGF1 alpha in both irradiated and nonirradiated animals. Finally, the sources of urinary cyclooxygenase products were investigated using an isogravitometric cross-perfusion system. These experiments demonstrated that urine TxB2 is derived from extrarenal sources, whereas 6-keto-PGF1 alpha is synthesized primarily by the kidney. It may be concluded that radiation exposure increases in vivo cyclooxygenase pathway activity by both renal and extrarenal tissues.