Chemical, experimental, and clinical studies on endogenous ouabain-like substance in hypertension.

A heat-stable, low molecular weight, anionic substance(s) capable of inhibiting 3H-ouabain binding and Na+-K+-ATPase activity could be extracted from human urine and plasma. The level of the inhibitor was elevated in 40%-50% of essential hypertensives, compared to controls, and also in some of the offspring of hypertensive parents. Higher levels of the inhibitor were measured in patients treated with beta-blocking agents than in those treated with diuretics. The inhibitor extracted from plasma also appeared capable of (1) inhibiting the uptake of serotonin in human platelets, an Na+-dependent mechanism, and (2) inducing an increase in blood pressure when injected intracerebroventricularly. From these various data, we propose that the increase in the endogenous inhibitor may play a role in essential hypertension and may modulate, at least partially, some of the various cell functions that depend on a transmembrane Na+ gradient, including cellular excitability.

Plasma endogenous sodium pump inhibitor in essential hypertension.

The presence of circulating Na+ pump inhibitors was investigated in hypertensive subjects using inhibition of ouabain binding to the pump and of Na+, K+-ATPase activity as tests. Plasma extracts from nearly half the normotensive subjects who were offspring of hypertensive parents as well as the essential hypertensive subjects were potent inhibitors. Three fractions, extracted from plasma, exhibited ouabain-like properties concerning competition for binding, inhibition of the Na+, K+-ATPase and of Na+-dependent serotonin uptake by platelets. When injected intracerebroventricularly, one of these fractions also induces a rise in blood pressure, as does ouabain. These results demonstrate the presence in some plasma of digitalis-like substances.