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 μm-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.