Ouabain was undetectable in any sample of plasma from either control subjects or patients with heart failure.40 These data, produced by particularly experienced workers, cannot be dismissed. Meanwhile the natriuretic action of ouabain / OLS could be disproved; in contrast according to … Aldosterone, sodium, and hypertension: lessons from torcetrapib? At an Endocrine Society meeting in 1995, opinions were divided as to whether authentic ouabain circulates in human plasma and is of adrenocortical origin.33 This debate was aired again and in considerably more detail in 199634,35 and in 2009.20,24 To summarize the major points of uncertainty in the latest of these debates,20,24 first, serious questions were raised regarding the physical evidence obtained in the early 1990s to support the authenticity of ouabain in human plasma; second, the ability of the human adrenals to produce immunoreactive ouabain had been called into question and details of the adrenal biosynthetic pathway remained to be defined; third, the DuPont/NEN ELISA kit for measuring ouabain was withdrawn from the market because of lack of commercial interest,24 which, we surmise, reflected widespread uncertainty as to what the assay was measuring; and fourth, the relatively sparse temporal profile of reports on EO contrasted with B-type natriuretic peptide, for example, which, since its discovery 3 years earlier than ouabain, had been the subject of a tsunami of reports based, in most cases, on well-established and widely available commercial assays. Under certain conditions, however, it was converted into its borate and/or other inorganic derivatives; the form in vivo adopted by ouabain is unknown. Customer Service The present study has revealed that treatment with ouabain at physiological concentrations is able to inhibit the migratory activities of human lung cancer H292 cells. High circulating levels of endogenous ouabain in the offspring of hypertensive and normotensive individuals. Following on from a criminal trial in Canada in which a nurse was accused of causing the death of a newborn when digoxin was discovered in the plasma despite the drug never having been prescribed, Valdes et al16 observed that immunoassayable digoxin was regularly present in neonatal plasma. We employed high resolution immunocytochemical techniques to localize alpha subunit isoforms in primary cultured rat astrocytes, neurons, and arterial myocytes. Main results of the ouabain and adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin. Evidence for an inhibitor of leucocyte sodium transport in the serum of neonates. Ouabain is only available on a doctor’s prescription and is produced in liquid form. The effect of expanding the blood volume of a dog on the short-circuit current across an isolated frog skin incorporated in the dog’s circulation. Ouabain decreases the frequency of heart seizures; this can be observed in daily practice and has also been sufficiently scientifically proved. Copyright 2013 - Knut Sroka - Disclaimer | Design - iSolutionz Media Support, „Ouabain“: the wasted opportunity to save heart patients. 1-800-AHA-USA-1 In the current brief review, we have focussed on a narrow component of this broad field: the question of whether, as claimed below, authentic ouabain or an isomer of ouabain is present in human circulation. Ouabain increases the number of apoptotic cells, induces autophagy, and upregulates Beclin-1 in Raji cells. organization. The intermediary pressor mechanism in the brain involves aldosterone biosynthesis, activation of mineralocorticoid receptors and increased epithelial sodium channel activity. This experience suggests that the characteristics of any antibody raised against such a substituted steroid needs to be investigated thoroughly to avoid confusion as to what the resulting immunoassay is actually measuring. Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), Journal of the American Heart Association (JAHA), Customer Service and Ordering Information, Basic, Translational, and Clinical Research. These results demonstrated differential roles of cav-1 in the regulation of ouabain signaling and contractility. Ouabain is not detectable in human plasma. Ouabain is only sold in Germany as a pharmaceutical product. Dr. Wieland Debusmann, who had a heart attack himself at the young age of 42, is an expert on ouabain. It was also shown that there was a crude correlation between the elevated blood pressure and the depression of the activity of the sodium pump as measured by the efflux rate constant.6 It was then clear that under certain conditions humans and other animals had the ability to secrete an inhibitor of the sodium pump and that this may well be of importance in the physiology/pathophysiology of salt overload, uremia, and essential hypertension. Proving that something does not exist, especially in a complex milieu such as plasma, is no easy matter. Hicks noted the only "fact" not found in relation to the body was evidence of vomiting. Is ouabain an authentic endogenous mammalian substance derived from the adrenal? First, there has been no substantial progress to address the question as to whether or not immunoreactive EO is produced by the adrenal glands in humans, and an adrenal biosynthetic pathway for EO remains to be established. No endogenous ouabain is detectable in human plasma by ultra-sensitive UPLC-MS/MS. © American Heart Association, Inc. All rights reserved. A recent article from workers in Germany has documented their attempt to do just that using state-of-the-art mass spectrometry.40 Their technique was rigorously validated and benefited from an internal standard of D3 ouabain where 3 of the hydrogen atoms are replaced by deuterium, giving a compound of virtually indistinguishable physical and chemical characteristics but with a mass of 587 as opposed to 584 Da for the natural compound. In 1975, it was shown that patients with essential hypertension had, as a group, reduced activity of the sodium pump of leukocytes, with corresponding elevated values for intracellular sodium.5 This finding proved to be reproducible in various laboratories, and once again the effect was transmissible by exposing normal cells to the plasma of hypertensives. The German pharmaceutical ouabain solutions are of good quality and the content is standardized. By continuing to browse this site you are agreeing to our use of cookies. On the one hand there are homeopathic ouabain preparations, such as “Strophactiv” D4 drops from the German company “magnet activ”, which are available via the Internet. Second, as mentioned already, articles continue to be published largely but not exclusively by workers at the University of Maryland and their colleagues claiming that EO not only exists but is of pathophysiological importance.24,25,29–32,37,38 It is a rare article amongst such papers that makes mention, even in passing, that there is some uncertainty regarding the structure and source of EO.39 Third and most importantly, as discussed below, recent evidence from German workers using techniques not available in the early 1990s contradicts the original reports in 1991 that authentic ouabain exists in human plasma.40, As an aside and in relation to the potential pathophysiological role of EO, it is worthy of note that, whereas some researchers have reported clearcut biological effects of administered authentic ouabain in various animal models and human, in particular to raise arterial pressure, other workers, including those in Christchurch, have failed to see such effects.20 In this regard and as summarized by Ferrari et al,41 the drug rostafuroxin that selectively displaces ouabain from the Na+, K+-ATPase receptor has been reported to lower arterial pressure in Milan hypertensive rats and select humans, and in deoxycorticosterone acetate salt hypertensive rats, it reduced blood pressure while also ameliorating endothelial dysfunction and oxidative stress in resistance arteries.42 These observations raised the possibility that if indeed EO exists and contributes to the development or maintenance of hypertension, inhibitors of EO mechanisms of action might provide a new class of antihypertensive drugs.42 When compared with placebo, however, rostafuroxin had no effect on systolic or diastolic pressure (using both office and 24-hour ambulatory recordings), plasma renin activity, 24-hour urinary sodium, and aldosterone excretion or plasma immunoreactive EO levels in 435 patients with systolic hypertension,43 although a subset of patients with a specific genetic profile was said to have shown an antihypertensive effect (data not shown). 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