Genetic basis of salt-susceptibility in the Sabra rat model of hypertension

Yoram Yagil, Chana Yagil

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14 Scopus citations

Abstract

The Sabra salt-sensitive SBH/y and salt-resistant SBN/y rats constitute a unique experimental model of hypertension in which salt-susceptibility is genetically determined and expressed only after salt-loading, without the development of spontaneous hypertension. To determine the genetic basis of salt-susceptibility in the Sabra rats, the candidate gene and total genome screen approaches were adopted. The likely candidate genes in this model incorporate salt-related physiological mechanisms such as the nitric oxide system, the arginine vasopressin axis and the epithelial sodium channel. In the random genome search scheme for culprit genes, SBH/y and SBN/y were cross-bred. A highly unusual and composite mode of transmission of salt- susceptibility was found in this cross, emphasizing the complexity of the genetic basis of salt-susceptibility. Linkage analysis of the entire rat genome with a large number of widely distributed microsatellite markers identified three putative gene loci on chromosomes 1 and 17 that contribute importantly to salt-sensitivity and/or resistance, and uncovered sex specificity in the role that salt-susceptibility genes fulfill in the 4development of hypertension.

Original languageEnglish
Pages (from-to)1493-1500
Number of pages8
JournalKidney International
Volume53
Issue number6
DOIs
StatePublished - 1 Jan 1998

Keywords

  • Arginine vasopressin
  • Candidate genes
  • Epithelial sodium channel
  • Genome screen
  • Hypertension
  • Linkage analysis
  • Microsatellites
  • Nitric oxide
  • Salt-susceptibility
  • Sexual dimorphism

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