Ouabain-like Na+,K(+)-ATPase inhibitory activity of a plasma extract in normal pregnancy and pregnancy induced hypertension.
To estimate the participation of a Na+,K(+)-ATPase-inhibiting plasma factor in pregnancy induced hypertension (PIH), the inhibitory activity and the characteristics of plasma extract eluted with ethanol through a C8 column were examined in normotensive non-pregnant women (N) and women with normal pregnancy (NP) and PIH. There were no differences among the 3 groups in the Na+,K(+)-ATPase activity of erythrocyte ghosts. The heat- and acid-stable plasma extract dose-dependently inhibited Na+,K(+)-ATPase activity with a pattern similar to that of ouabain, but different from that of vanadate. The inhibitory activity of plasma extract was not influenced by polyclonal digoxin antibody which almost completely prevented digoxin-induced inhibition and slightly but significantly reduced the ouabain-induced one. The results indicate that the plasma extract has ouabain-like inhibitory activity on Na+,K(+)-ATPase and that it is not endogenously synthesized digoxin itself, but a substance differing in structure from digoxin. Furthermore, the ouabain-like Na+,K(+)-ATPase inhibitory activity in NP plasma was significantly lower than that in PIH plasma, which was similar to that in N plasma. There were significant relationships between the ouabain-like Na+,K(+)-ATPase inhibitory activities in plasma and the diastolic and systolic blood pressures in NP and PIH groups. The results suggest that the lower ouabain-like Na+,K(+)-ATPase inhibitory activity in plasma probably participates in maintaining the blood pressure within the normal range during pregnancy and its failure may be involved in the genesis of PIH.
Miyagi
H
H
Department of Pharmacology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Higuchi
M
M
Nakayama
M
M
Moromizato
H
H
Sakanashi
M
M
D000328:Adult; D001794:Blood Pressure; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004077:Digoxin / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000201:enzymology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D010042:Ouabain / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D011247:Pregnancy / Q000097:blood*; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D014638:Vanadates; D010042:Ouabain; D004077:Digoxin; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase