The effect of chronic administration of digitoxin on the activity of the myocardial (Na + K)-ATPase in guinea-pigs.

When guinea-pigs were treated for 24 days with digitoxin 0.3 mg/kg s.c., the activity of the (Na + K)-ATPase of the heart muscle increased by about 30% compared to controls, whereas the enzymes prepared from kidney and brain showed no significant alteration in their activity. In animal species treated with digitoxin for 1 to 5 days, no increase of enzyme activity was observed. Only after 10 to 15 days of treatment, a significant increase of the (Na + K)-ATPase activity was noted which increased no further with treatment up to 24 days. There was no significant difference in the kinetic properties of the (Na + K)-ATPase prepared from digitoxin-treated animals compared to those from control animals; the KM-values for ATP remained unchanged, and there was the same dependence of the activity on the K+-concentration and the same sensitivity towards digitoxin. As there appears to be no significant change in the specific properties of the enzyme, the increase in activity may possibly be caused by an increase in the amount of enzyme as a result of an adaptive enzyme regulation.