Published online before print September 19, 2005, doi: 10.1161/01.HYP.0000184542.79324.d5
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(Hypertension. 2005;46:e13.)
© 2005 American Heart Association, Inc.
Hypertension Electronic Pages |
Oabain-Like Compound Changes Rapidly on Physical Exercise in Humans and Dogs
Worthing Hospital, Worthing, United Kingdom
The article by Bauer et al1 attempts to add further credence to the suggestion that ouabain or a ouabain-like compound is secreted in mammals. The results indicate that under conditions of stress, in this case exercise, there is a dramatic increase in the production of immunologically assayed ouabain. In the studied athletes, this increase was up to 36-fold when expressed as endogenous ouabain immunoreactivity and an 18-fold increase when assayed by inhibition of the sodium pump. Cessation of exercise resulted in a fall in the concentration of ouabain-like compounds with a half-life of 
3 to 5 minutes, and it is proposed that this is identical to the so-called 
-decay or rapid phase of ouabain clearance. This seems unlikely given this observed phenomenon follows bolus intravenous injection and is thought to reflect mixing in the intravascular compartment as well as the initial phase of tissue uptake.2 Also the half-life of ouabain measured in plasma has been quoted as between 5 and 50 hours. The data presented differ significantly from data provided by Lewis et al, in which a value for the half-life of plasma ouabain was obtained following bolus intravenous administration in humans.3 Under those conditions, the observed half-life of ouabain was at least 60 minutes as measured by high-performance liquid chromatography as well as by biological activity. Lewis et al also suggested that if ouabain is present in plasma it was at a concentration of less than 0.005 nmol/L, different by several orders of magnitude from the values quoted here. Bauer and colleagues have demonstrated some remarkable findings. However, they have not provided conclusive evidence that the biological or immunologic activity observed can be attributed to ouabain or, indeed, in a strict chemical sense, a ouabain-like compound.
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- Bauer N, Müller-Ehmsen J, Kramer U, Hambarchian N, Zobel C, Schwinger RHG, Neu H, Kirch U, Grünbaum E-G, Schoner W. Ouabain-like compound changes rapidly on physical exercise in humans and dogs. Hypertension. 2005; 45: 1024–1028.
[Abstract/Free Full Text] - Selden R, and Smith TW. Ouabain pharmacokinetics in dog and man. Circulation. 1972; 45: 1176–1182.
[Abstract/Free Full Text] - Lewis LK, Yandle TG, Lewis JG, A Mark Richards, Pidgeon GB, Kaaja RJ, and MGary Nicholls. Ouabain is not detectable in human plasma. Hypertension. 1994; 24: 549–555.
[Abstract/Free Full Text]
Response
Institute of Biochemistry and Endocrinology, Justus-Liebig University, Giessen, Germany
In his comment to the article of Bauer et al,1 Forni raises the following points: (1) The rapid decline of ouabain-like compound is unlikely equivalent with the rapid phase of ouabain-loss from plasma after its bolus injection. (2) The concentrations of ouabain measured by Lewis et al are significantly lower than those measured by us and not detectable in plasma.2
We are unable to comment on the findings of Lewis et al2, especially because a number of other groups found ouabain immunoreactivity in plasma correlating in 50% of whites with arterial blood pressure.3 Moreover, we could isolate ouabain from bovine adrenal glands and identify it by mass spectroscopy and 1H-NMR.4 Hence, it was essential for us to show that stress induced by physical exercise leads to rapid and significant changes of a ouabain-like compound in blood plasma. The rapid decline of the compound after the stop of exercise, with a half life of 3 to 5 minutes, is in the time frame seen after bolus injection of radioactive ouabain. This rapid phase of decline of injected ouabain quite probably includes an additional phenomenon recently described, namely the uptake of ouabain into the adrenal glands,5 in addition to the mixing process of intravascular compartments. This is the process we are mainly referring to in our discussion.
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TopReferencesReferences |
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- Bauer N, Müller-Ehmsen J, Kramer U, Hambarchian N, Zobel C, Schwinger RHG, Neu H, Kirch U, Grünbaum E-G, Schoner W. Ouabain-like compound changes rapidly on physical exercise in humans and dogs. Hypertension. 2005; 45: 1024–1028.
[Abstract/Free Full Text] - Lewis LK, Yandle TG, Lewis JG, Richards AM, Pidgeon GB, Kaaja RJ, Nicholls MG. Ouabain is not detectable in human plasma. Hypertension. 1994; 24: 549–555.
[Abstract/Free Full Text] - Hamlyn JM, Hamilton BP, Manunta P. Endogenous ouabain, sodium balance and blood pressure: a review and a hypothesis. J Hypertens. 1996; 14: 151–167.[CrossRef][Medline] [Order article via Infotrieve]
- Schneider R, Wray V, Nimtz M, Lehmann W-D, Kirch U, Antolovic R, Schoner W. Bovine adrenals contain, in addition to ouabain, a second inhibitor of the sodium pump. J Biol Chem. 1998; 273: 784–792.
[Abstract/Free Full Text] - Kitano S, Morimoto S, Nishibe A, Fukuo K, Hirotani A, Nakahashi T, Ysuda O, Ogihara T. Exogenous ouabain is accumulated in the adrenals and mimics the kinetics of endogenous digitalis-like factor in rats. Hypertens Res. 1998; 21: 47–56.[Medline] [Order article via Infotrieve]
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