Signalling pathways involving sodium pump stimulate endothelin-1 secretion and nitric oxide production in endothelial...

The cardiac steroid ouabain, a known inhibitor of the sodium pump, or Na+,K+-ATPase, has been shown to induce a variety of signaling cascades in various cells. The present study addresses the question of which signaling pathways are activated by ouabain in endothelial cells. Our findings indicate that ouabain, applied to human umbilical artery endothelial cells (HUAECs) in culture at low concentrations that do not cause global sodium pump inhibition, induces a reaction cascade that leads to the release of the vasoactive peptide endothelin-1 (ET-1). While ouabain-induced ET-1 release seems to be accomplished within 10 min, ouabain also stimulates a second signaling cascade that involves activation of Akt (also known as protein kinase B, or PKB), activation of endothelial nitric oxide synthase (eNOS) and increased NO production in HUAECs. This reaction cascade reaches its maximum approximately 30 min after exposure to the steroid. The results indicate that ouabain or similar compounds might actively participate in the regulation of vascular tone.