PGI2 production and angiotensin converting enzyme activity in cultured porcine pulmonary artery endothelial cells treated with paraquat.
The herbicide paraquat (PQ) is known to cause acute pulmonary edema at toxic dose and to induce morphologic changes in alveolar epithelial cells, even in the early phase of toxicity. However, whether the pulmonary vascular endothelial cells are specifically vulnerable to PQ is still controversial. To investigate the direct toxic and metabolic effects of PQ on pulmonary vascular endothelial cells, cultured porcine pulmonary artery endothelial cells (PPAEC) were evaluated. A dose of 10(-4) M of PQ inhibited the growth of endothelial cells. The thrombin- and bradykinin-stimulated production of prostacyclin (PGI2) by PPAEC was significantly enhanced, and the angiotensin converting enzyme (ACE) activity of cell lysate of PPAEC was significantly suppressed after incubation for 24 h with 10(-4) M PQ. No further enhancement of PGI2 production in response to thrombin after 48 h of incubation was demonstrated. These alterations in arachidonic acid metabolism and ACE activity did not result from the cytotoxicity of PQ, because the release of lactate dehydrogenase (LDH) into the culture medium increased only after 72 h incubation with PQ. Incubation for more than 48 h induced an obvious toxis effect on PPAEC.
2nd Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
N
N
Tamaru
K
K
Watanabe
M
M
Yoshida
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D011464:Epoprostenol / Q000096:biosynthesis*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects*; D011651:Pulmonary Artery / Q000166:cytology; D013552:Swine; D013917:Thrombin / Q000494:pharmacology
D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D007703:Peptidyl-Dipeptidase A; D013917:Thrombin; D010269:Paraquat; D001920:Bradykinin