title: Altered expression of renal aquaporins and α-adducin polymorphisms may contribute to the establishment of salt-sensitive hypertension.
abstract: BACKGROUND
  Sodium-sensitive hypertension is caused by renal tubular dysfunction, leading to increased retention of sodium and water. Previous findings have suggested that single-nucleotide polymorphisms of the cytoskeletal protein, α-adducin, are associated with increased membrane expression of the Na/K pump and abnormal renal sodium transport in Milan hypertensive strain (MHS) rats and in humans. However, the possible contribution of renal aquaporins (AQPs) to water retention remains undefined in MHS rats.
  
  
  METHODS
  Kidneys from MHS rats were analyzed and compared with those from age-matched Milan normotensive strain (MNS) animals by quantitative-PCR, immunoblotting, and immunoperoxidase. Endocytosis assay was performed on renal cells stably expressing AQP4 and co-transfected either with wild-type normotensive (NT) or with mutated hypertensive (HT) α-adducin.
  
  
  RESULTS
  Semiquantitative immunoblotting revealed that AQP1 abundance was significantly decreased only in HT MHS whereas AQP2 was reduced in both young pre-HT and adult-HT animals. On the other hand, AQP4 was dramatically upregulated in MHS regardless of the age. These results were confirmed by immunoperoxidase microscopy. Endocytosis assays clearly showed that the expression of mutated adducin strongly reduced the rate of constitutive AQP4 endocytosis, thereby increasing its abundance at the plasma membrane.
  
  
  CONCLUSIONS
  We provide here the first evidence that AQP1, AQP2, and AQP4 are dysregulated in the kidneys of MHS animals. In particular, we provide evidence that α-adducin mutations may be responsible for AQP4 upregulation. The downregulation of AQP1 and AQP2 and the upregulation of AQP4 may be relevant for the onset and maintenance of salt-sensitive hypertension.
authors: Department of General and Environmental Physiology, University of Bari, Bari, Italy. g.procino@biologia.uniba.it
authors: Giuseppe
authors: G
authors: Procino
authors: Francesca
authors: F
authors: Romano
authors: Lucia
authors: L
authors: Torielli
authors: Patrizia
authors: P
authors: Ferrari
authors: Giuseppe
authors: G
authors: Bianchi
authors: Maria
authors: M
authors: Svelto
authors: Giovanna
authors: G
authors: Valenti
mesh_terms: D000042:Absorption / Q000502:physiology; D000375:Aging / Q000502:physiology; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D020346:Aquaporins / Q000378:metabolism*; D001794:Blood Pressure; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D004705:Endocytosis / Q000502:physiology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains; D055049:Salt Tolerance / Q000235:genetics / Q000502:physiology*; D014867:Water / Q000378:metabolism; D000099291:Adducins
chemical_list: D051401:Aquaporin 4; D020346:Aquaporins; D002148:Calmodulin-Binding Proteins; D014867:Water; D000099291:Adducins; C496032:Aqp4 protein, rat