Effects of angiotensin-converting enzyme and angiotensin II on hypoxia-induced proliferation of cultured intra-pulmonary artery smooth muscle cells
Abstract
"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."
Keywords:
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."