Endogenous inhibition of red blood cell na, k-ATPase in essential and pregnancy-induced hypertension

Digoxin-like inhibitors of Na, K-ATPase have been implicated in the pathophysiology of essential(EH) and pregnancy-induced hypertension(PIH). A technique that enhances dissociation of digoxin from red blood cells(RBC) was used to displace endogenous digoxin-like substances from RBCs. RBC membranes were preincubated in Na and ATP(Release) or Na, K, Mg and ATP (Retention) prior to measuring ATPase activity. Groups studied were: 39 men with EH and 34 controls plus 10 women with PIH and 17 normotensive controls. All displayed similar increases in Na, K-ATPase activity (24.0±7.9% following Release. Plasma digoxin immunoreactivity(DI) was measured in pregnant women, m= 0.25±0.07 ng/ml. No DI was detected in nonpregnant women, but RBCs from these women demonstrated the same increase in Na, K-ATPase activity after Release. The 24% increase in activity achieved by Na and ATP preincubation can be reversed by adding K and Mg to the Release suspension. However, after RBC-bound digoxin is displaced by Release preincubation, addition of K and Mg cannot promote renewed binding and pump inhibition. Thus, the observed endogenous inhibition is not due to displacement of a digoxin-like substance but probably is related to alteration of the enzyme-membrane interaction. Furthermore, even though pregnant women demonstrate DI, an inhibitory susbstance with digoxin-like binding could not be recognized using theis technique.