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.
Feng
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X
Institute of Basic Medical Sciences, CAMS & PUMC, Beijing.
Cai
Y
Y
D000818:Animals; D002417:Cattle; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D004247:DNA; C072247:cyclo(Trp-Asp-Pro-Val-Leu)