This review concerns the structure of endogenous
ouabain, circulating levels of this
steroid in various disorders of fluid and electrolyte balance, recent evidence for the association of endogenous
ouabain with human
hypertension, the influence of
sodium and volume factors on
ouabain-induced
hypertension, and possible mechanisms for the hypertensinogenic activity of
ouabain.
CONCLUSIONS: The human circulation contains a closely related isomer of
ouabain of putative adrenocortical origin. Elevated circulating levels of this 'endogenous
ouabain' are common but not universal in physiologic and pathologic states associated with positive
sodium balance or
high blood pressure, or both. In the absence of adrenal hyperfunction, elevating circulating levels of endogenous
ouabain appear to be secondary to impaired renal clearance. Prolonged elevation of circulating
ouabain in the rat induces sustained
hypertension. This model exhibits normal plasma
renin activity, increased levels of
ouabain in the hypothalamus, pituitary, and kidney, and responds to
angiotensin converting enzyme inhibitor. In rats with normal kidney function,
ouabain-induced
hypertension is primarily
sodium-insensitive although maneuvers that hinder renal
sodium excretion augment the pressor effect of this
steroid. Prolonged administration of
ouabain into the brain ventricles augments sympathetic nervous system activity and induces sustained
hypertension. These observations lead us to propose the following hypothesis. Among Caucasian patients with
essential hypertension, a large fraction have elevated circulating levels of endogenous
ouabain, possibly caused by an inherited or acquired renal defect in clearance of this
steroid. In these patients, and in rats with
ouabain-induced
hypertension, increased local generation of, or increased target organ sensitivity to,
angiotensin II, or both, may contribute critically to heightened vasoconstriction and a sustained increase in blood pressure. Investigations of the efferent pressor mechanisms and the renal handling of endogenous
ouabain are novel approaches to the etiology and
therapy of several common cardiovascular disorders.