Document Detail

The ouabain-binding site of the α2 isoform of Na,K-ATPase plays a role in blood pressure regulation during pregnancy.
MedLine Citation:
PMID:  20940714     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: The cardiotonic steroid-binding site of the α2 Na,K-ATPase plays a role in maintaining normal SBP during pregnancy.
Naomi Oshiro; Iva Dostanic-Larson; Jon C Neumann; Jerry B Lingrel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-09
Journal Detail:
Title:  American journal of hypertension     Volume:  23     ISSN:  1941-7225     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-16     Completed Date:  2011-03-03     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1279-85     Citation Subset:  IM    
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
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MeSH Terms
Binding Sites
Blood Pressure / drug effects,  physiology*
Brain / enzymology
Kidney / enzymology
Myocardium / enzymology
Ouabain / metabolism
Sodium-Potassium-Exchanging ATPase / genetics,  metabolism*,  physiology
Grant Support
Reg. No./Substance:
630-60-4/Ouabain; EC 3.6.1.-/Atp1a2 protein, mouse; EC ATPase

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