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Elevated Arterial Pressure, Vascular Wall “Waterlogging,” and Impaired Cardiac Growth in Rats Chronically Receiving Digoxin 1

Abstract Decreased activity of the sarcolemmal sodium pump may account, in part, for the elevated arterial pressure and also for the vascular wall “waterlogging” in certain forms of hypertension. To further test this hypothesis, digoxin, 120 or 240 mg/kg/day, was administered orally to 4-week-old rats and continued for 6-7 weeks in Group A rats. After 5 weeks 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 to 660 ng/ml. In rats receiving digoxin, tail systolic arterial pressures measured three times per week were slightly (6%) but significantly (P <0.001) higher than in control rats. At age 12 weeks, tail systolic pressures (mm Hg; M ± SEM) were 128.2 ± 1.1, 118.4 ± 0.7, and 118.0 ± 0.3 in Groups A, B, and C. At age 12-13 weeks, 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 weight and LV weight/body wt in Group A rats were decreased by 4-9% (P <0.05). These data indicate that, in rats, chronic inhibition of the membrane sodium pump in the cardiovascular muscle by digitalis is associated with increased arterial pressure and vascular wall waterlogging. Thus, pump inhibition may play a role in similar abnormalities occurring in hypertension. Digoxin administration also impaired cardiac growth in these young rats.