Vascular endothelium as a target for endogenous ouabain: studies on the effect of ouabain on human endothelial cells.
It has been suggested that an endogenous inhibitor of the sodium pump, identified as ouabain, contributes to the regulation of blood pressure and the pathogenesis of certain forms of hypertension. Vascular endothelial cells, whose functional integrity is crucial for the maintenance of blood flow and the antithrombotic activity, could be a target for endogenous ouabain. We studied the effect of ouabain on human umbilical vein endothelial cells (HUVEC) and found that nanomolar concentrations of the glycoside have an antiapoptotic activity that is dependent on the activation of phosphatidylinositol 3 kinase (PI-3K) and extracellular signal-regulated kinases (ERKs). At the same concentrations we found that ouabain affects the endocytosis of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) through the activation of signaling proteins such as Src kinase. This review sumarizes our findings on the effect of ouabain on HUVEC, the signal transduction pathways involved and the significance of these observations on the pathophysiology of endothelial function.
Trevisi
L
L
Department of Pharmacology and Anaesthesiology Egidio Meneghetti University of Padua, Padua, Italy. lucia.trevisi@unipd.it
Pighin
I
I
Luciani
S
S
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002301:Cardiac Glycosides / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D010042:Ouabain / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013778:Tetrazolium Salts / Q000737:chemistry / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D002301:Cardiac Glycosides; D048049:Extracellular Signal-Regulated MAP Kinases; D010042:Ouabain; D019869:Phosphatidylinositol 3-Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D013778:Tetrazolium Salts; D013844:Thiazoles; D019061:src-Family Kinases; C022616:thiazolyl blue