17 beta-Oestradiol inhibits stimulated endothelin release in human vascular endothelial cells

Wynn Department of Metabolic Medicine, Imperial College School of Medicine, National Heart and Lung Institute, London, UK.

Oestrogen is believed to possess cardiovascular protective properties. Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen for vascular smooth muscle cells. We have investigated release of ET-1 from human endothelial cells in response to 17 beta-oestradiol. Serum was found to stimulate significantly ET-1 release during the first 4 h of culture. 17 beta-Oestradiol significantly reduced ET-1 immunoreactivity in the media of treated cells by up to 49% of control values after 4 h. This effect was found to be inversely related to the dose of 17 beta-oestradiol. Significant dose-dependent increases in nitric oxide synthase expression were observed in response to oestrogen after 24 h but not after 4 h. Serum-free experiments demonstrated that low doses of oestrogen were able to inhibit thrombin-induced ET-1 release whilst supraphysiological levels did not. These results provide a further perspective on the ability of oestrogens to maintain vascular health.