[Effects of endogenous nitric oxide on pulmonary artery hypertension and lung injury induced by endotoxin].

Changes in mean artery pressure (MAP), pulmonary artery pressure (PAP) and nitric oxide (NO) contents in inflow and outflow pulmonary blood(IPB,OPB) were observed after endotoxin lipopolysacchride (LPS) was injected i.v. in rabbits. Changes of PAP and lung injury were also observed after inhibitor of NO synthesis L-NNA or inhibitor of inducible NO synthesis AG was pre-injected by vein. The results showed that MAP decreased significantly after LPS administration, and 0.5-2h later PAP showed some increase (P<0.05) being maximum at PAP (1h) during which the content of NO in IPB was detectably decreased but NO in OPB did not. NO contents in OPB at 3h and in IPB and OPB at 5h increased significantly following LPS administration as compared with control.PAP correlated negatively with NO in IPB at the time before and 1h after LPS injection, which did not exist at 3 and 5h after LPS injection. After L-NNA pretreatment, when PAP elevated significantly, the MDA content in IPB and OPB also showed significant increase, while animal survival rate fell significantly. Light microscopic examination showed severe alveolar atelectasis, significant congestion and sequestration of leukocytes in lung tissue. When pretreated with AG, MAP elevated significantly in 3-5h, PAP remained unchanged. The MDA content in blood was lower at 5h in the LPS injected group with less pathological changes in lung tissue at 5h compared with the LPS group. The above results suggested that there was pulmonary hypertension in the early stage after endotoxin administration. The decrease of NO content in IPB may be one of the mechanisms underlying pulmonary artery hypertension(PAH).NO seemed to alleviate PAH and lung injury at the early stage after endotoxin administration. When iNOS was induced at the later stage, NO contributed to lung injury caused by endotoxin.