Hypoxia and endothelin-1 stimulate DNA synthesis of pulmonary artery smooth muscle cells.

Hypoxia and endothelin-1 (ET-1) are associated with constriction of pulmonary vasculature both in vivo and in vitro. However, the role of hypoxia and ET-1 in the vascular remodelling during the development of pulmonary hypertension is unclear. This study demonstrated that ET-1 (0.1 nmol/L to 100 nmol/L) increased the [3H] thymidine uptake in a dose-dependent manner in cultured bovine pulmonary artery smooth muscle cells (PASMC), which was enhanced by exposing PASMC to hypoxia (2% O2, 93% N2, 5% CO2). BQ123, the specific antagonist of endothelin receptor subtype A, eliminated the ET-1 medicated proliferation of PASMC and the cooperative effect of hypoxia. Some dilatory drugs could inhibit the mitogenic effect of ET-1. We also observed that hypoxia significantly increased [3H]thymidine uptake in PASMC without ET-1 and BQ123 could inhibit this effect. Radioimmunoassay suggested that there was an autocrine of ET-1 in cultured PASMC which was enhanced by hypoxia significantly.