Ouabain-Like and Non-Ouabain-Like Factors in Plasma of Patients with Essential Hypertension

Abstract

Circulating inhibitor of Na+,K+-ATPase and ouabain-like immunoreactivity were studied in patients with essential hypertension. In the plasma of patients, two types of Na+,K+-ATPase inhibitors (ouabain-like and non-ouabain-like inhibitors) and ouabain-like immunoreactivity were detected. Ouabain-like inhibitor was clearly detected at a low KCl concentration (0.1 mM) in the assay buffer, and non-ouabain-like inhibitor was detected at a high KCl concentration (10 mM). The plasma level of ouabain-like inhibitor correlated significantly with that of ouabain-like immunoreactivity (p less than 0.001) and with a mean blood pressure (p less than 0.01). The plasma level of non-ouabain-like inhibitor was not correlated with the levels of either ouabain-like immunoreactivity or mean blood pressure. The level of plasma ouabain-like inhibitor did not correlate with that of plasma non-ouabain like inhibitor. Both ouabain-like inhibitor and ouabain-like immunoreactivity in the plasma of patients with essential hypertension were significantly higher than those in normotensive subjects, but the plasma level of non-ouabain-like inhibitor in patients with essential hypertension was not higher than that in normotensive subjects. These results suggest that the plasma from patients with essential hypertension contains ouabain-like factor(s) which is important to maintain the high blood pressure.

Identification and characterization of a ouabain-like compound from human plasma.

“…Our finding of elevated plasma OLC in hypertension is consistent with that in patients with primary aldosteronism and essential hypertension (38,39).…”

“…Increased levels of humoral Na+ transport inhibitors have been detected during plasma volume expansion (13,31,32) and in hypertension (13,23,(33)(34)(35)(36)(37)(38)(39). Our finding of elevated plasma OLC in hypertension is consistent with that in patients with primary aldosteronism and essential hypertension (38,39).…”

Ouabain treatment increases nitric oxide bioavailability and decreases superoxide anion production in cerebral vessels

“…Mammalian circulation contains a cardiac glycoside that is putatively of adrenocortical origin and that is structurally similar to the prototypical inhibitor of the sodium pump, ouabain [2]. Circulating levels of this compound as well as ouabain-like immunoreactivity are increased in many forms of hypertension, including essential hypertension [3,4], and there is potential for the development of Na þ pump modulators as antihypertensive drugs [5]. Moreover, chronic administration of exogenous ouabain is known to induce hypertension in rats [6][7][8][9][10][11][12][13][14] and mice [15].…”

Effects of an endogenous ouabainlike compound on heart and aorta.

“…- 21 Also, patients with essential hypertension 21 and primary aldosteronism 22 have elevated plasma levels of a substance with ouabainlike immunoreactivity. In all of these patients with established hypertension, the levels of the ouabainlike immunoreactivity and of the sodium pump inhibitor can be directly correlated with blood pressure.…”