Adducin in essential hypertension

Paolo Manunta, Cristina Barlassina, Giuseppe Bianchi

Research output: Contribution to journalArticlepeer-review

Abstract

In Milan hypertensive rats (MHS) the sequence of events going from renal function to cell membrane ion transport abnormalities and finally to the molecular defect responsible of hypertension has been established. A polymorphism of the cytoskeletal protein adducin has been identified as a likely culprit for hypertension in these rats. Two point mutations in MHS α- (F316Y) and β- (Q529R) adducin genes have been shown to be associated with hypertension in genetic crosses of MHS and MNS rats. Also in humans, a polymorphism of α-adducin gene (Gly460Trp) has been found to be significantly associated both to hypertension and salt sensitivity. Studies aimed at clarifying the functional role of α-adducin variants have shown that adducin from the MHS rats is able to stimulate Na-KATPase activity both after transfection in renal tubular cells and after incubation with the enzyme in a cell-free system. Also the human hypertensive α-adducin variant displays the same activity of MHS adducin in a cell-free system. Therefore, both in humans and in rats, adducin polymorphisms may affect blood pressure and kidney function by modulating the overall capacity of tubular epithelial cells to transport ions, through variations of the Na-KATPase activity. However, adducin polymorphisms account for only a portion of hypertension both in humans and rats. Therefore additive or epistatic interactions with other genes involved in renal sodium handling need to be studied.

Original languageEnglish
Pages (from-to)41-44
Number of pages4
JournalFEBS Letters
Volume430
Issue number1-2
DOIs
Publication statusPublished - Jun 23 1998

Keywords

  • Cytoskeleton
  • Genetic
  • High blood pressure
  • Na-KATPase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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