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 substance with digoxin-like binding could not be recognized using this technique.