Long-term ouabain administration produces 3 hypertension in rats

Christina M. Yuan, Paolo Manunta, John M. Hamlyn, Shanwan Chen, Erin Bohen, Jane Y Yeun, Francis J. Haddy, Motilal B. Pamnani

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

Ouabain has recently been identified as an endogenous Na+-K+ pump inhibitor. We administered ouabain chronically to normotensive rats with varying degrees of reduced renal mass (RRM) and to normal two-kidney rats to see whether hypertension could be produced. Normal male Wistar rats and rats with 25%, 60%, and 70% RRM received ouabain (13.9 μg/kg per day IP) in normal saline for 4 weeks followed by ouabain (27.8 μg/kg per day IP) for 3 to 4 more weeks. Respective control animals received vehicle only. Blood pressure was recorded weekly by tail plethysmography. Animals received tap water and standard rat chow, except for 70% RRM rats, which received distilled water and sodium-free chow. After 6 to 8 weeks of treatment, with rats under thiobutabarbital anesthesia, direct blood pressure was determined. Plasma, tissue, and urinary ouabain levels were measured with a specific radioimmunoassay. Animals receiving ouabain developed significant increases in mean blood pressure compared with control animals (70% RRM, 147±4 vs 116±4 mm Hg; 60% RRM, 140±4 vs 107±3 mm Hg; 25% RRM, 131±5 vs 100±2 mm Hg; no RRM, 116±4 vs 98±5 mm Hg). Plasma ouabain levels measured 24 hours after the last ouabain dose were not different in animals receiving ouabain vs those receiving vehicle. However, kidney tissue ouabain levels were significantly greater (6.39±1.17 vs 2.36±0.52 μg/kg, P<.05) in animals receiving ouabain. In conclusion, ouabain, given chronically, is associated with the development of hypertension in RRM rats as well as in normal rats. Blood pressure was greater in animals with greater degrees of RRM for a given ouabain dose.

Original languageEnglish (US)
Pages (from-to)178-187
Number of pages10
JournalHypertension
Volume22
Issue number2
StatePublished - Aug 1993
Externally publishedYes

Keywords

  • Hypertension, renal
  • Na,K-ATPase
  • Ouabain
  • Sodium-potassium pump

ASJC Scopus subject areas

  • Internal Medicine

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  • Cite this

    Yuan, C. M., Manunta, P., Hamlyn, J. M., Chen, S., Bohen, E., Yeun, J. Y., Haddy, F. J., & Pamnani, M. B. (1993). Long-term ouabain administration produces 3 hypertension in rats. Hypertension, 22(2), 178-187.