¹Laboratory for Molecular Medicine and Department of Nephrology and Hypertension, Barzilai Medical Center, Ashkelon, and Faculty of Health Sciences, Ben-Gurion University, Beer Sheba, Israel

Correspondence: Yoram Yagil, Laboratory for Molecular Medicine, Department of Nephrology and Hypertension, Barzilai Medical Center, Ashkelon 78306, Israel. E-mail: labmomed@bgumail.bgu.ac.il

Abstract

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