title: DOCA-salt hypertension does not require the ouabain-sensitive binding site of the α2 Na,K-ATPase.
abstract: 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: α(R/R)α2(S/S)), α1-resistant, α2-resistant (α1(R/R)α2(R/R)) and α1-sensitive, α2-resistant (α1(S/S)α2(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 α1(R/R)α2(R/R) mice developed hypertension to the same extent as α1(R/R)α2(S/S) mice (wild type), and the α1(S/S)α2(R/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 α1(R/R)α2(S/S) or α1(R/R)α2(R/R) mice. However, the α2 subunit was expressed at substantially higher levels in the hearts of α1(R/R)α2(R/R) than α1(R/R)α2(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 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.
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Ohio, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Lorenz
authors.forename: Naomi
authors.initials: N
authors.lastname: Oshiro
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Loreaux
authors.forename: Jerry B
authors.initials: JB
authors.lastname: Lingrel
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002018:Bufanolides / Q000097:blood; D003900:Desoxycorticosterone; D004077:Digoxin / Q000276:immunology; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007140:Immunoglobulin Fab Fragments; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology*; D012965:Sodium Chloride; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D002018:Bufanolides; D007140:Immunoglobulin Fab Fragments; C050199:digoxin antibodies Fab fragments; C093896:marinobufagenin; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D010042:Ouabain; D004077:Digoxin; C401838:Atp1a2 protein, mouse; C497344:Atp1a1 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase