Tamaru N, Watanabe K, Yoshida M
2nd Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1993 Apr;48(4):291-6. doi: 10.1016/0952-3278(93)90218-l.
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.
已知除草剂百草枯（PQ）在中毒剂量时会导致急性肺水肿，并在毒性早期诱导肺泡上皮细胞发生形态学变化。然而，肺血管内皮细胞是否对PQ特别敏感仍存在争议。为了研究PQ对肺血管内皮细胞的直接毒性和代谢作用，对培养的猪肺动脉内皮细胞（PPAEC）进行了评估。10^(-4) M的PQ剂量抑制了内皮细胞的生长。用10^(-4) M PQ孵育24小时后，PPAEC受凝血酶和缓激肽刺激产生的前列环素（PGI2）显著增强，PPAEC细胞裂解物的血管紧张素转换酶（ACE）活性显著受到抑制。孵育48小时后，未显示出对凝血酶反应的PGI2产生进一步增强。这些花生四烯酸代谢和ACE活性的改变并非由PQ的细胞毒性引起，因为只有在与PQ孵育72小时后，培养基中乳酸脱氢酶（LDH）的释放才增加。孵育超过48小时对PPAEC产生明显的毒性作用。
