Endogenous digitalis: pathophysiologic roles and therapeutic applications

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Abstract
Interest in endogenous digitalis-like factors or 'cardiotonic steroids' has increased as a result of the identification of such factors in humans and the delineation of a mechanism by which these hormones signal through the sodium/potassium-transporting ATPase. The authors of this Review, who have both spent more than 20 years conducting research on this topic, examine the role of endogenous cardiotonic steroids in the pathophysiology of renal and cardiovascular disease. They also highlight potential therapeutic strategies involving modulation of cardiotonic steroids. Endogenous digitalis-like factors, also called cardiotonic steroids, have been thought for nearly half a century to have important roles in health and disease. The endogenous cardiotonic steroids ouabain and marinobufagenin have been identified in humans, and an effector mechanism has been delineated by which these hormones signal through the sodium/potassium-transporting ATPase. These findings have increased interest in this field substantially. Although cardiotonic steroids were first considered important in the regulation of renal sodium transport and arterial pressure, subsequent work has implicated these hormones in the control of cell growth, apoptosis and fibrosis, among other processes. This Review focuses on the role of endogenous cardiotonic steroids in the pathophysiology of essential hypertension, congestive heart failure, end-stage renal disease and pre-eclampsia. We also discuss potential therapeutic strategies that have emerged as a result of the increased understanding of the regulation and actions of cardiotonic steroids.