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.
Ringel
R
R
Department of Pediatrics, University of Maryland School of Medicine, Baltimore.
Pinkas
G
G
Hamlyn
J
J
Mullins
L
L
Hamilton
B
B
D000328:Adult; D004077:Digoxin / Q000378:metabolism / Q000627:therapeutic use; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000201:enzymology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013223:Statistics as Topic
D004077:Digoxin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase