The Ouabain-Binding Site of the 2 Isoform of Na,K-ATPase Plays a Role in Blood Pressure Regulation During Pregnancy

Abstract

The cardiotonic steroid/ouabain-binding site of the α subunit of Na,K-ATPase is thought to play an important role in cardiovascular homeostasis. Previously, we demonstrated the cardiotonic steroid-binding site of the α2 Na,K-ATPase is involved in adrenocorticotropic hormone (ACTH)-induced hypertension by using gene-modified α2(R/R) mice in which the cardiotonic steroid-binding site is relatively resistant to ouabain compared to the ouabain-sensitive wild-type α2(S/S) mice. To further explore the importance of this site in the cardiovascular system, we investigated blood pressure regulation during pregnancy in mice with the α2(R/R) isoform. The systolic blood pressure (SBP) of the α2(S/S) and α2(R/R) mice was measured before and during pregnancy by tail-cuff. The expression of the α isoforms of Na, K-ATPase in various tissues and plasma endogenous ouabain contents were assessed prior to pregnancy as well as days 7 and 17 of gestation. The α2(S/S) mice showed a gradual decrease in the SBP during the first two trimesters, followed by an increase above the preconceptional level in the third trimester. However, the α2(R/R) mice exhibited a lower blood pressure in the third trimester. The cardiac expression of the α2 Na,K-ATPase in the α2(S/S) mice was significantly less than that of the α2(R/R) mice throughout the pregnancy. The plasma endogenous ouabain concentration significantly increased by twofold at day 17 of pregnancy in the α2(R/R) mice but not in the α2(S/S) mice. The cardiotonic steroid-binding site of the α2 Na,K-ATPase plays a role in maintaining normal SBP during pregnancy.