We investigated the effects of low ouabain concentrations on systolic (SAP) and diastolic (DAP) arterial pressures and on pressor reactivity in 3-month-old male spontaneously hypertensive rats (SHR). Arterial blood pressure (BP) and pressor reactivity to phenylephrine (PHE) were investigated before and after 0.18 μg/kg ouabain administration (N = 6). The influence of hexamethonium (N = 6), canr...

T he concept of a circulating digitalis-like inhibitor of the sodium pump, Na + , K +-ATPase, evolved from studies performed in the 1960s. De Wardener et al 1 addressed the question of whether a small increase in the glomerular filtration rate together with changes in the concentration of the more recently discovered hormone aldosterone could explain the natriuresis that generally followed salt...

TO THE EDITOR: In the article “Why isn’t endogenous ouabain more widely accepted?” (2), Mordecai P. Blaustein refers to Thomas Kuhn in stating that scientists tend to ignore ideas and data that don’t fit their preconceptions and often don’t even read (or digest) articles that fall outside their “comfort zone.” Such a behavior is certainly true for many scientists engaged in research on endogeno...

A 6.5-kilobase fragment of genomic DNA from mutant mouse cells under ouabain selection pressure conferred ouabain resistance when transfected into ouabain-sensitive CV1 green monkey fibroblasts. Ouabain resistance was induced in the presence of 10 microM ouabain. Amiloride (500 microM) completely blocked ouabain-insensitive 86Rb+ uptake into these cells. Plasma membranes from these cells demons...

The cardiac glycoside ouabain, which is a specific inhibitor of the Na+,K+-pump, confers dramatic protection from the cytotoxic effects of doxorubicin (Adriamycin). This effect was documented in cultured A549 cells (human lung adenocarcinoma). CCL210 cells (human fibroblasts), and V79 cells (hamster fibroblasts). Maximum protection from doxorubicin cytotoxicity was achieved using 1 microM ouaba...

Dostanic, Iva, Richard J. Paul, John N. Lorenz, Steven Theriault, James W. Van Huysse, and Jerry B. Lingrel. The 2-isoform of Na-K-ATPase mediates ouabain-induced hypertension in mice and increased vascular contractility in vitro. Am J Physiol Heart Circ Physiol 288: H477–H485, 2005. First published September 30, 2004; doi:10.1152/ajpheart.00083.2004.—Although ouabain is known to induce hyperte...

Ouabain has recently been reported to be an endogenous mammalian substance released by the adrenal cortex and present in normal plasma. We have attempted to confirm and extend this observation. Using a ouabain radioimmunoassay developed in this laboratory, we fractionated by high-performance liquid chromatography (HPLC) normal human plasma from healthy volunteers to determine the presence of ou...

In the present studies we have explored the relation between ouabain binding and the inhibition of potassium influx in intact human erythrocytes. The rate at which bound ouabain molecules dissociate from the erythrocyte membrane is not altered by complete replacement of choline with sodium or by partial replacement with potassium. These findings indicate that the effects of these cations on oua...

CIonal assays for CFU-S, CFU-C, BFU-E, and CFU-E were employed to evaluate the effect of ouabain on the proliferation of mouse hematopoietic progenitor cells. Preincubation of bone marrow cells with ouabain at concentrations of 101_1012 M suppressed the proliferation of CFU-S as measured by the spleen colony assay. At lO9Mouabain, spleen colony formation was inhibited by more than 95%. When inc...

Cardiac arrhythmias and cardiac arrest were induced in pentobarbitone anaesthetised cats by slow intravenous infusion of ouabain. The dose of ouabain required for the induction of the stages of arrhythmias and cardiac arrest and the maximum pressor effect induced by ouabain were assessed in control and clonidine pretreated cats. Clonidine caused significant delay in the onset of cardiotonic eff...