血管紧张素转化酶和血管紧张素Ⅱ对低氧促培养的肺内小动脉平滑肌细胞增殖作用的影响

目的：研究局部血管紧张素转化酶及血管紧张素Ⅱ和低氧促进肺动脉平滑肌细胞增殖作用之间的关系。方法：分离培养肺内小动脉平滑肌细胞,测定[^3H]thymidine掺入和细胞计数作为细胞增殖的指标。结果：低氧显著促进培养的肺内小动脉平滑肌细胞增殖,其[^3H]thymidine掺入和细胞计数分别增加166．6％（P＜0．01）和52．0％（P＜0．01）。captopril和losartan预处理可显著抑制低氧对肺内小动脉平滑肌细胞增殖的促进作用,[^3H]thymidine掺入分别被抑制51．3％（P＜0．01）和49．8％（P＜0．01）,细胞计数分别被抑制22．2％（P＜0．01）和17．％（P＜0．01）。而PD－123319基本无明显作用。结论：肺内小动脉平滑肌细胞局部血管紧张素转化酶的过度表达及血管紧张素Ⅱ在低氧促平滑肌细胞增殖中发挥重要作用。

Effects of angiotensin-converting enzyme and angiotensin II on hypoxia-induced proliferation of cultured intra-pulmonary artery smooth muscle cells

AIM: To investigate whether local angiotensin-converting enzyme (ACE) and endogenous angiotensin II (ANG II) are involved directly in the proliferation of intra-pulmonary artery smooth muscle cells (PASMC) induced by hypoxia. METHODS: Smooth muscle cells isolated from rabbit intra-pulmonary artery (300-400 microns-diameter) were cultured and used in the 3-8 passages. [3H]Thymidine incorporation and cell counts were used to measure PASMC proliferation. RESULTS: Exposure of PASMC to hypoxia for 24 h resulted in an increase in the [3H]thymidine incorporation and cell number by 166.6% and 52.0% as compared with normoxia (P < 0.01). Treatment with either captopril or losartan markedly inhibited the increase, compared with the control, [3H]thymidine incorporation was inhibited by 51.3% (P < 0.01) and 49.8% (P < 0.01) and cell number was inhibited by 22.2% (P < 0.01) and 17.9% (P < 0.01), respectively, while PD-123319 showed no significant effect. CONCLUSION: Local overexpression of PASMC ACE and ANG II play an important role in the proliferation of PASMC induced by hypoxia.