Endogenous ouabain in renal Na(+) handling and related diseases

Abstract

The Na(+) pump and its Endogenous modulator Ouabain (EO) can be considered as an ancestral enzymatic system, conserved among species ranging from Drosophila to humans, related to Na handling. In this review, we examine how EO is linked with vascular function in hypertension and if it impacts the pathogenesis of heart and renal failure. Moreover, the molecular mechanism of endogenous ouabain-linked hypertension involves the sodium pump/sodium-calcium exchanger duet. Biosynthesis of EO occurs in adrenal glands and is under the control of angiotensin II, ACTH and epinephrine. Elevated concentrations of EO and in the sub-nanomolar concentration range were found to stimulate proliferation and differentiation of cardiac and smooth muscle cells. They may have a primary role in the development of cardiac dysfunction and failure. Experimental data suggest that the Na/K-ATPase α(2)-catalytic subunit causes EO-induced vasoconstriction. Finally, maneuvers that promote Na depletion, as diuretic therapy or reduced Na intake, raise the EO levels. Taken together, these findings suggest a key role for EO in body Na homeostasis.

Conflict of interest statement

Conflict of interests

None of the authors has a con3ict of interest with regard to the data presented in this manuscript.

Copyright © 2010 Elsevier B.V. All rights reserved.

Figures

Fig. 1

The relationship between sodium balance and circulating EO is described by a J-shaped curve: acute and chronic diuretic treatment, furosemide and HCTZ, (Negative Na balance), raise EO; at steady state of body Na balance (Normal) the circulating EO returns to basal values; during high-salt diet or acute volume expansion (Positive) the natriuretic effect is present in those with increased EO.