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(Hypertension. 1997;30:753.)
© 1997 American Heart Association, Inc.

Articles

Role of Ouabain-like Compound in the Regulation of Transmembrane Sodium and Potassium Gradients in Rats

Atsuo Goto; Kaoru Yamada; Hiroshi Nagoshi; Yoshiyuki Dan; Masao Omata

From the Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, and the Department of Human Dry Dock, Sanraku Hospital (K.Y.), Tokyo, Japan.

Correspondence to Atsuo Goto, MD, Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.

Abstract A major biologically active Na,K-ATPase inhibitor in the mammalian body may be ouabain-like compound. We investigated the potential roles of circulating ouabain-like compound in the regulation of Na⁺ and K⁺ homeostasis in terms of Na⁺ and K⁺ distribution between the cells and the extracellular fluid (internal balance). First, we developed a population of rats immunized against ouabain to block the action of ouabain-like compound. We measured plasma and intracellular Na⁺ and K⁺ concentrations in skeletal muscle and determined Na⁺ (extracellular-to-intracellular concentration ratio) and K⁺ (intracellular-to-extracellular concentration ratio) gradients in immune rats. We examined also the ability to respond to hypertonic NaCl load in immune rats. Consistent lower plasma K⁺ levels and steeper Na⁺ and K⁺ gradients were observed in immune rats. K⁺ handling in response to hypertonic NaCl load was altered, and lower plasma K⁺ level was maintained in immune rats. Second, we used PST-2238, a newly developed anti-ouabain agent, to block the action of ouabain-like compound and examined its effect on plasma Na⁺ and K⁺ concentrations. Chronic administration of PST-2238 significantly lowered plasma K⁺ levels in rats with subtotal nephrectomy. These findings collectively suggest that ouabain-like compound may determine at least in part the internal Na⁺ and K⁺ distribution and the transmembrane cation gradients in vivo in rats.

Key Words: Na,K-ATPase • sodium • potassium • ouabain • sodium pump

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