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


CONCLUSIONS
Local overexpression of PASMC ACE and ANG II play an important role in the proliferation of PASMC induced by hypoxia.
Yu
T Z
TZ
Laboratory of Cardiovascular Physiology, Hunan Medical University, Changsha 410078, China. tianzheng_yu@163.net
Ma
C T
CT
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia; D002478:Cells, Cultured; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011651:Pulmonary Artery / Q000166:cytology; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D000804:Angiotensin II; C073402:PD 123319; D002216:Captopril; D019808:Losartan