Ouabain-induced hypertension in the rat: relationships among plasma and tissue ouabain and blood pressure


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Abstract

ObjectivesTo determine the steady-state dose-dependence of blood pressure, plasma and tissue ouabain during continuous infusion of ouabain in the rat, and to evaluate the adrenal dependence and effect of a high salt intake on this form of hypertension.Design and methodsOuabain was administered, via subcutaneous osmotic pumps, to normal and adrenalectomized male Sprague-Dawley rats for 5 weeks. Blood pressure, plasma renin and aldosterone, and circulating and tissue levels of ouabain were determined.ResultsFollowing a latent period, blood pressures and circulating ouabain were significantly elevated dose-dependently in glycoside-infused rats at 5 weeks. Upon withdrawal of the ouabain infusion, blood pressure and plasma ouabain levels normalized within 1 week. In rats that received 30$mUg ouabain/kg per day, the circulating, kidney, hypothalamic and anterior pituitary levels of ouabain were increased significantly (by 7-, 15-, 2.8− and 2.1-fold, respectively), whereas the content of other tissues tested was unchanged. Blood pressure and plasma levels of ouabain correlated with hypothalamic and kidney glycoside content in the infused rats. High-performance liquid chromatography of the adrenal, renal, hypothalamic and pituitary extracts showed one major peak of ouabain immunoreactivity, with a retention time equivalent to that of commercial ouabain. Plasma renin activity was normal, whereas aldosterone levels were increased significantly to 2.9− and sevenfold in rats that received 10 and 30$mUg ouabain/kg per day, respectively. Dietary salt loading suppressed aldosterone and did not exacerbate hypertension. In bilaterally adrenalectomized rats the ambient circulating and kidney levels of ouabain were low and ouabain infusion raised glycoside levels and blood pressure significantly.ConclusionsProlonged infusion of ouabain in the normal rat raises the circulating, kidney, hypothalamic and anterior pituitary levels and induces a reversible hypertension with normal plasma renin activity. Although characterized by raised aldosterone levels, the hypertension does not require the adrenal glands and is not salt-sensitive. This model may be useful for exploring novel mechanisms of long-term regulation of blood pressure.

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