缺氧对培养的肺动脉内皮细胞血管紧张素Ⅱ分泌的影响

缺氧是否通过影响血管内皮细胞的分泌功能而参与缺氧性肺动脉高压的发生尚不清楚。本实验动态观察了缺氧对培养的新生小牛内皮细胞（ＰＡＥＣ）的血管紧张素Ⅱ（ＡＴⅡ）分泌的影响。结果发现：２．５％Ｏ２缺氧早期（１．５ｈ），ＰＡＥＣ的ＡＴⅡ分泌增加（Ｐ＜０．０１ｖｓ常氧组），缺氧后期与常氧组无明显差别；０％Ｏ２缺氧早期（１．５－６ｈ），ＡＴⅡ分泌明显降低（Ｐ＜０．０１ｖｓ常氧组及２．５％Ｏ２组），后期ＡＴⅡ分泌明显增高（Ｐ＜０．０１ｖｓ常氧组及２．５％Ｏ２组）；无论缺氧还是常氧条件下，ＮＯ供体ＳＩＮ１显著抑制ＡＴⅡ的分泌（Ｐ＜０．０１），而内源性ＮＯ抑制剂硝基精氨酸则明显促进ＡＴⅡ分泌（Ｐ＜０．０１）；０％Ｏ２缺氧２４ｈ后，ＰＡＥＣ细胞内ｃＧＭＰ含量明显降低（Ｐ＜０．０５）。上述结果表明缺氧可通过抑制ＰＡＥＣ的内源性ＮＯ产生而促进ＡＴⅡ的分泌，ＰＡＥＣ自分泌的改变可能参与缺氧性肺动脉高压的发生过程。

The effects of hypoxia on angiotensin II secretion by cultured pulmonary artery endothelial cells]

The alterations of paracrine function of pulmonary arterial endothelial cells (PAEC) might play an important role in the development of hypoxic artery hypertension (HPAH). To test this hypothesis, the effects of hypoxia on angiotensin II (AT II) secretion by new born bovine PAEC were investigated. AT II secretion increased significantly when PAECs were incubated under 2.5% O2 hypoxic condition for 1.5 h (P < 0.01 vs control). But it decreased from 1.5 h to 12 h incubation and increased from 12 h to 48 h incubation under 0% O2 hypoxic condition, with significance compared with control group (P < 0.01). NO donor SIN-1 inhibited but endogenous NO inhibitor L-nitro-arginine promoted AT II secretion significantly under both normorxic and hypoxic conditions. It was also found that the concentration of cyclic guanine monophosphate in PAEC decreased significantly at 24 h incubation in 0% O2. The above results suggest that changes of AT II in PAEC may participate in the development of HPAH.