Hypertension, Vol 22, 178-187, Copyright © 1993 by American Heart Association
CM Yuan, P Manunta, JM Hamlyn, S Chen, E Bohen, J Yeun, FJ Haddy and MB Pamnani
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 micrograms/kg per
day IP) in normal saline for 4 weeks followed by ouabain (27.8
micrograms/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
micrograms/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.
ARTICLES
Long-term ouabain administration produces hypertension in rats
Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md.
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