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Endogenous Ouabain: A Link Between Sodium Intake and Hypertension

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Abstract

The sodium pump, an ancestral enzyme with conserved ability to bind ouabain, plays a key role in salt conservation and is regulated by aldosterone and endogenous ouabain (EO). Plasma EO is elevated in about 45% of patients with essential hypertension and correlates with blood pressure. The relationship of EO with Na+ balance is complex. Na+ depletion raises circulating EO, whereas acute saline loads have no effect on EO in essential hypertension, and ambient levels of EO are unrelated to the saline sensitivity of blood pressure. Short-term periods of high dietary salt elevate EO and the relationship with salt balance in normal individuals is V-shaped, whereas the long-term relationship is likely to be L-shaped. Normal individuals suppress the high EO transient triggered by high-salt diets and avoid hypertension. In contrast, patients with elevated EO on normal Na+ intakes have hypertension related to poor modulation of EO biosynthesis, clearance, or both.

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Acknowledgments

This work was supported in part by USPHS grants HL75584, HL045215, and HL0788705 (JMH) and by European Union grants LSMH-CT-2006-037093 InGenious HyperCare and HEALTH-F4-2007-201550 HyperGenes (PM).

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, University of Maryland, 655 West Baltimore Street, Baltimore, MD, 21201, USA

    John M. Hamlyn

  2. Nephrology, Dialysis and Hypertension Division, Scientific Institute San Raffaele, Università “Vita-Salute” San Raffaele, Via Olgettina 60, 20132, Milan, Italy

    Paolo Manunta

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Correspondence to John M. Hamlyn.

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Hamlyn, J.M., Manunta, P. Endogenous Ouabain: A Link Between Sodium Intake and Hypertension. Curr Hypertens Rep 13, 14–20 (2011). https://doi.org/10.1007/s11906-010-0161-z

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