Regulation of endothelin-1 production in deoxycorticosterone acetate- salt-treated endothelial cells.

ABSTRACT

The aim of this study was to investigate the direct effect of deoxycorticosterone acetate (DOCA) on the expression of endothelin-1 (ET-1) mRNA and production of ET-1 peptides in cultured bovine carotid endothelial cells (BCEC) and human umbilical vein endothelial cells (HUVEC). The mineralocorticoid, DOCA, was administered to BCEC and HUVEC with or without additional salt (200 mmol/l). The ET-1 mRNA was elevated to 150% and 180% after a 24-hour incubation with DOCA (5 micromol/l) in BCEC and HUVEC, respectively. Intracellular content of ET-1 peptides of BCEC and HUVEC was increased from 21.66 +/- 0.3 to 23.64 +/- 0.19 fmol/10(5) cells and from 8.38 +/- 0.82 to 11.26 +/- 0.91 fmol/10(5) cells, respectively, in the DOCA-conditioned medium. Also, DOCA treatment for 24 h increased the secretion of ET-1 peptide from 1.62 +/- 0.17 to 5.33 +/- 0.67 fmol/10(5) cells in BCEC and from 0.95 +/- 0.08 to 3.56 +/- 0.36 fmol/10(5) cells in HUVEC. In DOCA-salt-treated endothelium, regulation of ET-1 gene was similar to that with DOCA alone. The DOCA-induced increase in expression of ET-1 mRNA and the ET-1 peptide level were both diminished in dexamethasone (DEX, 10 nmol/l)- or mifepristone (RU486, 0.5 micromol/l)-treated endothelium. These results suggest that DOCA directly increased the ET-1 mRNA expression in endothelium and could be mediated in part by a glucocorticoid receptor pathway which was independent of salt and hyperosmolarity.