The ouabain-like sodium pump inhibitor in mammals (so-called "endogenous ouabain") has been considered a subtle structural isomer of ouabain. Its structural investigation, however, has long been hindered by the paucity of sample material. Our recent purification of endogenous ouabain (3 micrograms) from bovine hypothalamus allowed the measurement of its 1H-NMR. The obtained spectrum as well as ...

BACKGROUND An endogenous digitalis-like compound in mammals has long been postulated, but only recently has a substance indistinguishable from ouabain been identified in human plasma. Because of the potential significance of such a substance in patients with congestive heart failure, we sought to evaluate the pathophysiology of endogenous ouabain in these individuals. METHODS AND RESULTS Usin...

The structural characterization of the ouabain-like sodium pump inhibitor in mammals (so-called `endogenous ouabain') has long been hindered by the paucity of the sample material. While many microscale structural analyses, including LC/MS and sugar analysis, could not differentiate `endogenous ouabain' from ouabain, our past nanogram-scale `pentanaphthoylation' followed by HPLC and circular dic...

Although ouabain is known to induce hypertension, the mechanism of how this cardiac glycoside affects blood pressure is uncertain. The present study demonstrates that the alpha2-isoform of the Na-K-ATPase mediates the pressor effects of ouabain in mice. To accomplish this, we analyzed the effect of ouabain on blood pressure in wild-type mice, where the alpha2-isoform is sensitive to ouabain, an...

Cardiotonic glycosides, like ouabain, inhibit Na(+)-K(+)-ATPase. Recent evidence suggests that low molar concentrations of ouabain alter cell growth. Studies were conducted to examine the effect of ouabain on Akt phosphorylation and rate of cell proliferation in opossum kidney (OK) proximal tubule cells. Cells exposed to 10 nM ouabain displayed increased Akt Ser(473) phosphorylation, as evidenc...

Whether a given dose of ouabain will produce inotropic or toxic effects depends on factors that affect the apparent affinity (K0.5) of the Na/K pump for ouabain. To accurately resolve these factors, especially the effect of intracellular Na concentration (Nai), we have applied three complementary techniques for measuring the K0.5 for ouabain in cultured embryonic chick cardiac myocytes. Under c...

Renin-angiotensin and endothelin systems are involved in the cardiovascular effects produced by treatment with ouabain. We recently demonstrated that the contractile response to phenylephrine is decreased in ouabain-treated rats. The present study investigated whether endothelin-1 (ET-1) and angiotensin II (Ang II) contributes to the vascular changes observed in rats chronically treated with ou...

To assess whether chronic ouabain administration causes hypertension by increasing sympathetic activity, we recorded arterial blood pressure and heart rate at rest and after ganglionic blockade in conscious Wistar rats following 10 to 14 days of central or peripheral administration of ouabain. Intracerebroventricular or intravenous infusion of ouabain (10 micrograms/d for both) as well as subcu...

It was reported recently that the endogenous digitalis-like factor ouabain may mainly originate from the adrenal gland. To ascertain the pathophysiological significance of endogenous ouabain and to examine if it originates in the adrenal gland, we determined plasma immunoreactive ouabain levels in patients with various cardiovascular and endocrine diseases. Plasma immunoreactive ouabain levels ...

In current research reports several disease states are claimed to be associated with elevated levels of endogenous ouabain. These include hypertension, cardiac enlargement, cardiac and renal failure, and a variety of terminal disorders. It has been suggested that endogenous ouabain should be considered as a major contributor to increased blood pressure and overall cardiovascular risk. These hyp...