6-keto prostaglandin F1 alpha and thromboxane B2 in isolated, buffer-perfused lungs from monocrotaline pyrrole-treated rats.

Monocrotaline pyrrole (MCTP) causes pulmonary endothelial cell injury and pulmonary hypertension in rats. Damage to endothelial cells in culture has been associated with altered prostacyclin (PGI2) production; therefore, it was of interest to determine if MCTP affected pulmonary PGI2 production. Release of the stable metabolites of PGI2 and thromboxane A2, 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and thromboxane B2 (TxB2), respectively, was examined in isolated, buffer-perfused lungs from MCTP-treated rats at times when elevated pulmonary arterial pressure is first observed (day 7) and when the pulmonary hypertensive state has existed for some time (day 14), 6-keto PGF1 alpha release was not affected by MCTP treatment 7 or 14 days after a single intravenous injection of MCTP. TxB2 release was also unaffected at day 7, however 14 days after treatment TxB2 release was greater in lungs from MCTP-treated rats compared to controls. The concentration of both 6-keto PGF1 alpha and TxB2 increased when arachidonic acid was infused into lungs from control or treated rats. These data indicate that MCTP treatment increases the release of TxB2 from isolated lungs at a time when pulmonary hypertension is well-established, but not during early development of pulmonary hypertension.