ENDOGENOUS OUABAIN, SODIUM-BALANCE AND BLOOD-PRESSURE - A REVIEW AND A HYPOTHESIS

Objective To assess possible relationships between endogenous ouabain, sodium balance and blood pressure. Content This review concerns the s tructure of endogenous ouabain, circulating levels of this steroid in various disorders of fluid and electrolyte balance, recent evidence fo r the association of endogenous ouabain with human hypertension, the i nfluence 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 lev els of this 'endogenous ouabain' are common but not universal in physi ologic and pathologic states associated with positive sodium balance o r high blood pressure, or both. In the absence of adrenal hyperfunctio n, elevating circulating levels of endogenous ouabain appear to be sec ondary to impaired renal clearance, Prolonged elevation of circulating ouabain in the rat induces sustained hypertension, This model exhibit s normal plasma renin activity, increased levels of ouabain in the hyp othalamus, pituitary, and kidney, and responds to angiotensin converti ng enzyme inhibitors, In rats with normal kidney function, ouabain-ind uced hypertension is primarily sodium-insensitive although maneuvers t hat hinder renal sodium excretion augment the presser effect of this s teroid. Prolonged administration of ouabain into the brain ventricles augments sympathetic nervous system activity and induces sustained hyp ertension. These observations lead us to propose the following hypothe sis. Among Caucasian patients with essential hypertension, a large fra ction 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 hypertens ion, increased local generation of, or increased target organ sensitiv ity to, angiotensin II, or both, may contribute critically to heighten ed vasoconstriction and a sustained increase in blood pressure, Invest igations of the efferent presser mechanisms and the renal handling of endogenous ouabain are novel approaches to the etiology and therapy of several common cardiovascular disorders.