Journal Article

DOCA-salt hypertension does not require the ouabain-sensitive binding site of the α2 Na,K-ATPase

John N. Lorenz, Naomi Oshiro, Elizabeth L. Loreaux and Jerry B. Lingrel

in American Journal of Hypertension

Published on behalf of American Journal of Hypertension, Ltd.

Volume 25, issue 4, pages 421-429
Published in print April 2012 | ISSN: 0895-7061
Published online April 2012 | e-ISSN: 1941-7225 | DOI: https://dx.doi.org/10.1038/ajh.2011.255
DOCA-salt hypertension does not require the ouabain-sensitive binding site of the α2 Na,K-ATPase

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Background

We have shown that the ouabain-sensitive α2 Na,K-ATPase is required for adrenocorticotropic hormone (ACTH)-induced hypertension and gestational blood pressure regulation. It is therefore of interest to explore whether this binding site participates in the development of other forms of hypertension, such as deoxycorticosterone acetate (DOCA)-salt using mutant mice with altered sensitivity to ouabain.

Methods

Wild-type (α1 ouabain-resistant, α2 ouabain-sensitive: αR/Rα2S/S), α1-resistant, α2-resistant (α1R/Rα2R/R) and α1-sensitive, α2-resistant (α1S/Sα2R/R) mice were uninephrectomized and implanted with DOCA pellets. The animals were given either tap water or 1% NaCl, and blood pressure was measured before and after DOCA.

Results

DOCA-salt-treated α1R/Rα2R/R mice developed hypertension to the same extent as α1R/Rα2S/S mice (wild type), and the α1S/Sα2R/R mice given DOCA-salt also showed no difference from the other two genotypes. The expression of the α1 isoform was not changed by DOCA-salt treatment in either α1R/Rα2S/S or α1R/Rα2R/R mice. However, the α2 subunit was expressed at substantially higher levels in the hearts of α1R/Rα2R/R than α1R/Rα2S/S mice, regardless of treatment. Plasma levels of ouabain did not change consistently, but those of marinobufagenin were modestly higher in DOCA-salt treated mice relatively to those without salt.

Conclusions

The ouabain-binding site of either the α1 or α2 Na,K-ATPase subunit does not play an essential role in the development of DOCA-salt hypertension in this mouse model. These findings indicate that the underlying mechanisms of hypertension induced by DOCA-salt treatment are different from those of ACTH-induced hypertension.

Keywords: blood pressure; cardiotonic steroids; hypertension; marinobufagenin

Journal Article.  5992 words.  Illustrated.

Subjects: Clinical Skills ; Cardiovascular Medicine

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