[Effects of hypoxia on the morphology and proliferation of cultured pulmonary arterial smooth muscle cell].

The effects of hypoxia (2.5% O2 and/or < 1% O2) on bovine pulmonary arterial smooth muscle cell (PASM) proliferation and phenotype change were investigated using immunocytochemical analysis and H- TdR incorporation. The results showed that hypoxia initiated the change of PASM from contractile phenotype to synthetic phenotype. The synthetic phenotype smooth muscle cell was characterized by increase in endoplasmic reticulum and mitochondria, and by decrease in alpha-actin and muscle fiber at the end of 24 h hypoxia. Then the endoplasmic reticulum became dilated, the mitochondria became swollen and myelin figure appeared after 48 h hypoxic exposure. PASM 3H-TdR incorporation was decreased at the end of 6 h hypoxia (P < 0.05), then increased gradually at the end of 12 h. PASM DNA synthesis was significantly stimulated by 24 h hypoxia (P < 0.05). Flow cytometric DNA analysis revealed that hypoxia induced significant enhancement of G2/M phase of PASMs, decreased G0/G1 phase of PASMs (P < 0.001), and only increased S phase of PASMs in 12 h anoxia group (P < 0.05), but decreased S phase of PASMs from 24 h to 48 h (P < 0.001). Immunocytochemical reaction of proliferating cell nuclear antigen (PCNA) in PASM under anoxic condition was more stronger than that of normoxic PASM at 24 h. These results suggest that hypoxia may at first inhibit and then stimulate PASM proliferation and induce phenotype change, which may lead to the development of hypoxic pulmonary hypertension.