Induction of adrenomedullin by hypoxia in cultured human coronary artery endothelial cells

To explore the role of adrenomedullin (ADM) in pathophysiology of ischemic heart disease, we investigated the effects of hypoxia on the production and secretion of ADM in cultured human coronary artery endothelial cells. Treatment with hypoxia (5% CO2/94% N-2/1% O-2) for 6 and 12 h increased expression levels of ADM mRNA 2.2-fold and fivefold compared with the normoxia control, respectively. The levels of immunoreactive ADM in the media were increased by 12-h hypoxia about fivefold compared with the control (39.0 +/- 1.1 fmol/10(5) cells per 12 h under hypoxia and 7.9 +/- 0.4 fmol/10(5) cells per 12 h under normoxia; P < 0.01, n = 4, mean +/- SEM). Reverse-phase high-performance liquid chromatography of the extracts of culture media under normoxia and hypoxia showed one major peak eluting in the position of human ADM standard. The production and secretion of ADM were increased in cultured human coronary artery endothelial cells under hypoxia, ADM may therefore play an important pathophysiological role in ischemic heart disease. (C) 1999 Elsevier Science Inc. All rights reserved.