Elevated Arterial Pressure, Vascular Wall "Waterlogging," and Impaired Cardiac Growth in Rats Chronically Receiving Digoxin

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Abstract
Decreased activity of the sarcolemmal Na pump may account, in part, for the elevated arterial pressure and for the vascular wall waterlogging in certain forms of hypertension. To further test this hypothesis, digoxin, 120 or 240 mg/kg per day, was administered orally to 6-wk-old rats and continued for 6-7 wk in group A rats. After 5 wk of similar administration, digoxin was stopped in group B rats. Group C control rats never received digoxin. Measured serum digoxin levels in group A rats ranged from 204-660 ng/ml. In rats receiving digoxin, tail systolic arterial pressures measured 3 times/wk were slightly (6%) but significantly (P < 0.001) higher than in control rats. At age 12 wk, tail systolic pressures were 128.2 .+-. 1.1, 118.4 .+-. 0.7 and 118.0 .+-. 0.3 mm Hg in groups A, B and C, respectively. At age 12-13 wk, water content of the thoracic vena cava in digoxin-treated rats of group A was increased by 3-5% (P < 0.05). An additional finding was that left ventricular [LV] weight and LV wt/body wt in group A rats were decreased by 4-9% (P < 0.05). In rats, chronic inhibition of the membrane Na pump in the cardiovascular muscle by digitalis is associated with increased arterial pressure and vascular wall waterlogging. Pump inhibition may play a role in similar abnormalities occurring in hypertension. Digoxin administration impaired cardiac growth in these young rats.