摘要：In this study we found: 1, There was endogenous ONOO- formation in lungs in the early stage of endotoxic shock. Exogenous ONOO- led to increase in microvascular permeability, severe lung pathological changes and enhanced MDA content. 2, It was, for the first time, found that responses of isolated pulmonary artery preincubated with ONOO- showed abnormal manifestations. (1) Low dose of ONOO- let to the inhibition of endothelial dependent relaxation, but enhacement of contractile response, both of which were similar to changes of reactivity in isolated pulmonary artery induced by LPS. (2) High dose of ONOO- reduced contractile response to PE and relaxation to SNP. 3, ONOO- had direct effect for relaxation of precontracted isolated pulmonary artery. The relaxing action of ONOO- was weak and was negtively regulated by endothelial cells, supporting the notion that ONOO- may be involved in pulmonary hypertension in the early stage of endotoxic shock. 4, It was, for the first time, found that LPS-induced increase in endogenous ONOO- generation in BPAEC and that endogenous ONOO- mediated injury to BPAEC induced by LPS, which may be a novel mechanism for endotoxin-elicited damage to endothelial cells. 5, Exposure of pulmonary artery to LPS led to reduction in endothelial dependent relaxation but enhancement in contractile response, both of which were reversed by concomitant exposure to CCK and LPS. 6, CCK protected cultured BPAEC against the detrimental effects of LPS such as lipoperoxide damages and cellular apoptosis as well as LPS-induced endogenous ONOO- formation. The underlying mechanism of CCK for cytoprotection may be mediated by its receptors and related to its reduced ability of endothelia to generate ONOO- induced by LPS.