IMR Press / FBL / Volume 10 / Issue 3 / DOI: 10.2741/1711

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

The endogenous ouabain: molecular basis of its role in hypertension and cardiovascular complications
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1 Prassis sigma-tau Research Institute, Settimo Milanese, 20019 Milan, Italy
2 Division of Nephrology, Dialysis and Hypertension, Vita e Salute University, San Raffaele Hospital, 20132 Milan, Italy

Academic Editor: Joseph Shapiro

Front. Biosci. (Landmark Ed) 2005, 10(3), 2472–2477;
Published: 1 September 2005
(This article belongs to the Special Issue Regulation and function of NaK-ATPase in health and disease)

Elevated levels of the endogenous ouabain (EO), a closely related isomer of ouabain, are implicated in rat and human hypertension and in related cardiovascular complications. The pathogenetic mechanisms through which EO affects the cardiovascular system involve the modulation of the renal Na/K-ATPase, implicated in renal tubular sodium reabsorption, and the activation of signal transduction pathways, promoting the transcription of growth-related genes. Experimental and clinical evidence on rats and humans stimulated the pharmacological research for developing novel anti-hypertensive agents able to antagonize the cellular and molecular alterations mediated by EO. Among them, the digitoxigenin derivate, PST 2238, has been selected for its ability to antagonize the ouabain-induced effects on blood pressure and organ hypertrophy at oral doses of µg/kg/day in vivo. The pharmacological selectivity and safety of PST 2238 suggests that the compound may be effective for the treatment of those forms of hypertension in which renal sodium handling alterations and cardiovascular complications are associated with increased production of EO.

Endogenous Ouabain
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