Hypoxia stimulates prostacyclin generation by dog lung in vitro.
We have investigated the possibility that pulmonary biosynthesis of prostacyclin and thromboxane A2 (TXA2) may be affected by variations in PO2. Fresh lung homogenated from 8 dogs were incubated for 1 hour at 37 degrees C in Krebs-Ringer solution, at high (492 mmHg) or low (53 mmHg) PO2. After incubation, the stable metabolites of prostacyclin (6-keto-PGF1) and of TXA2 (TXB2) were measured by radioimmunoassay. The basal ("pre-incubation") levels of these metabolites, measured in tubes in which biosynthesis was arrested by the addition of indomethacin (10 g/ml), were 0.76 +/- 0.15 and 0.76 +/- 0.11 ng/mg wet wt. for 6-keto-PGF1 alpha, in high and low PO2, respectively, and 0.97 +/- 0.09 and 0.82 +/- 0.15 x 10(-1) ng/mg wet wt. for TXB2, in high and low PO2 respectively. Synthesis during incubation in other tubes was estimated by subtracting basal values from those measured at the end of incubation. More 6-keto-PGF1 alpha was formed in homogenates exposed to low PO2 (3.01 +/- 0.45) than in those exposed kept at high PO2 (1.89 +/- 0.37, p less than 0.001), but equal amounts of TXB2 were bound under both conditions. These results suggest that hypoxia may stimulate pulmonary prostacyclin synthesis; a pulmonary vasodilator, prostacyclin may help modulate hypoxic vasoconstriction in the lung.
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D004285:Dogs; D011464:Epoprostenol / Q000096:biosynthesis*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000032:analysis
D011453:Prostaglandins; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007213:Indomethacin