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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.

Paraquat is a herbicide known to cause pulmonary edema in its acute toxic phase. Many investigators showed that paraquat induces morphological changes of alveolar epithelial cells even in its early phase. Controversy still exists, however, as to whether pulmonary vascular endothelial cells are also morphologically vulnerable to paraquat. To test the direct toxicity and metabolic changes of pulmonary vascular endothelial cells after paraquat addition, porcine pulmonary artery endothelial cells (PPAEC) were cultured. Thrombin- or bradykinin-stimulated PGI2 production was enhanced significantly, and the angiotensin converting enzyme (ACE) activity of cell lysate of PPAEC was significantly suppressed after a 24-hour incubation with 10(-4) M of paraquat. No further thrombin-induced enhancement of PGI2 production was noted after a 48-hour incubation. The alterations in arachidonic acid metabolism and ACE activity mentioned above did not result from cytotoxicity of paraquat because LDH release into culture medium was not increased during 72 hours of incubation with paraquat. Longer incubation more than 48 hours, in turn, induces obvious toxic effects on PPAEC.

The activity of angiotensin converting enzyme (ACE) in cell lysate of cultured human umbilical vein endothelial cells (HUVEC) after a 24-hour incubation with 10(-3) and 10(-4)M of paraquat (PQ) was decreased. However, LDH released into the culture medium of HUVEC during the 24-hour incubation with PQ was not increased. Many investigators show that the change in serum ACE activity reflects the impairment of vascular endothelial cells. We showed in this report that ACE was decreased even at an early stage of endothelial injury induced by PQ, when LDH release is not yet increased.