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缺氧时培养的肺动脉平滑肌细胞血管紧张素Ⅱ自分泌的变化及其机制

王培勇, 刘健, 于中和, 许蜀闽, 罗德成, 孙秉庸

第三军医大学高原医学研究室病理生理教研室. 重庆 400038；新桥医院心内科. 重庆 400037；北京军区总医院呼吸科. 北京100700；北京医科大学心血管基础研究所. 北京 100083

摘要

缺氧是否通过影响血管平滑肌细胞的自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肺动脉平滑肌细胞(PASMCs)的血管紧张素Ⅱ(ATⅡ)分泌的影响。结果发现：2.5％O_(2)缺氧导致PASMCs的ATⅡ分泌降低(P＜0.01vs常氧组），0％O_(2)缺氧进一步抑制ATⅡ分泌(P＜0.01。常氧组及2.5％O_(2)组)。常氧条件下，NO供体SIN-1显著的抑制ATⅡ的分泌(P＜0.01)，而NO合酶抑制剂硝基精氨酸(LNA)则能消除缺氧对ATⅡ分泌的抑制作用(P＜0.01)。0％O_(2)缺氧24h后，PASMCs细胞内cGMP含量显著增多(P＜0.05)，这一改变可被LNA所抑制。0％O_(2)缺氧使PASMCs的~(3)H－TdR掺入显著增多(P＜0.001)，常氧培养的PASMCs加入10~(-6)mol／L的开搏通(captopril)培养24h,其~(3)H-TdR掺入显著减少(P＜0.001)，缺氧培养的PASMCs加入10~(-6)mol／L的captopril,其~(3)H-TdR参入与缺氧组相比无显著变化。上述结果表明，缺氧可通过诱导PASMCs的内源性NO产生而抑制ATⅡ的分泌，PASMCs自分泌ATⅡ的降低可能参与缺氧性肺动脉高压的发生。

关键词： 缺氧; 平滑肌细胞; 肺血管 血管紧张素Ⅱ; 一氧化氮; 环核苷酸

Changes of angiotensin ii autocrine by cultured pulmonary artery Smooth muscle cells exposed to anoxia

Wang Peiyonc, Liu Jian, Yu Zhong He, Xu Shumin, Luo Decheng, Sun Bingyong

Research Laboratory of High Altitude Medicine，Department of Pathophysiology，Third Military Medical College. Chongqing 400038,China

Abstract

Alterations of autocrine function of pulmonary arterial smooth muscle cells (PASMCs) might play an important role in development of hypoxic pulmonary hypertension (HPH). To test this hypothesis, the effects of hypoxia on angiotensin Ⅱ(AT Ⅱ) secretion by cultured new born bovine PASMCs were investigated. AT Ⅱ secretion decreased significantly when PASMCs were incubated under 2.5% O_(2) hypoxic condition for 3 to 48 h (P<0.01 vs control),but decreased boer under anoxic conditi0n (P<0.01 vs control and 2.5% O_(2) group). Nitric oxide (NO) donor SIN-1 inhibited AT Ⅱ secretion significantly under normoxic condition, but NO synthase inhihitor L-nitro-arginine (LNA) eliminated the inhibitory effect of anoxia on AT Ⅱ autocrine and promoted AT Ⅱ release. lt was also found that the concentration of cGMP in PASMCs increased singnificantly (P<0.01) at 24 h incubation in 0% O_(2), an effect that can be attenuated by LNA.

Key words: Hypoxia;Smooth muscle;Pulmonary artery;Angiotensin Ⅱ;Nitric oxide

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引用本文：

王培勇, 刘健, 于中和, 许蜀闽, 罗德成, 孙秉庸. 缺氧时培养的肺动脉平滑肌细胞血管紧张素Ⅱ自分泌的变化及其机制[J]. 生理学报 1998; 50 (2): .

Wang Peiyonc, Liu Jian, Yu Zhong He, Xu Shumin, Luo Decheng, Sun Bingyong. Changes of angiotensin ii autocrine by cultured pulmonary artery Smooth muscle cells exposed to anoxia. Acta Physiol Sin 1998; 50 (2): (in Chinese with English abstract).