| First Author | Lorenz JN | Year | 2012 |
| Journal | Am J Hypertens | Volume | 25 |
| Issue | 4 | Pages | 421-9 |
| PubMed ID | 22258333 | Mgi Jnum | J:324980 |
| Mgi Id | MGI:6882039 | Doi | 10.1038/ajh.2011.255 |
| Citation | Lorenz JN, et al. (2012) DOCA-salt hypertension does not require the ouabain-sensitive binding site of the alpha2 Na,K-ATPase. Am J Hypertens 25(4):421-9 |
| abstractText | BACKGROUND: We have shown that the ouabain-sensitive alpha2 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 (alpha1 ouabain-resistant, alpha2 ouabain-sensitive: alpha(R/R)alpha2(S/S)), alpha1-resistant, alpha2-resistant (alpha1(R/R)alpha2(R/R)) and alpha1-sensitive, alpha2-resistant (alpha1(S/S)alpha2(R/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 alpha1(R/R)alpha2(R/R) mice developed hypertension to the same extent as alpha1(R/R)alpha2(S/S) mice (wild type), and the alpha1(S/S)alpha2(R/R) mice given DOCA-salt also showed no difference from the other two genotypes. The expression of the alpha1 isoform was not changed by DOCA-salt treatment in either alpha1(R/R)alpha2(S/S) or alpha1(R/R)alpha2(R/R) mice. However, the alpha2 subunit was expressed at substantially higher levels in the hearts of alpha1(R/R)alpha2(R/R) than alpha1(R/R)alpha2(S/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 alpha1 or alpha2 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. |
