Original papers: Genetic aspectsIdentification of salt-sensitive genes in the kidneys of Dahl ratsLighthall, Geoffrey Ka,d; Hamilton, Bruce Pb,c; Hamlyn, John Ma Author Information Departments of aPhysiology and bMedicine, University of Maryland, cVeterans Administration Medical Center, Baltimore, Maryland and dDepartment of Anesthesiology, Stanford University School of Medicine, Stanford, California, USA. Sponsorship: Supported in part by a Veterans Administration Merit Award to B.P.H. Correspondence and requests for reprints to John M. Hamlyn, PhD, Department of Physiology, School of Medicine, University of Maryland, 655 West Baltimore Street, Baltimore, Maryland 21201, USA. Tel: +1 410 706 3479; fax +1 410 706 8341; e-mail: [email protected] Received 16 September 2003 Revised 7 April 2004 Accepted 16 April 2004 See editorial commentary on page 1461 Journal of Hypertension 22(8):p 1487-1494, August 2004. | DOI: 10.1097/01.hjh.0000133719.94075.e2 Buy Metrics Abstract Objective Inherited differences in renal function underlie the effect of high salt diets on blood pressure in Dahl rats. We probed the kidneys of inbred Dahl SS/Jr and SR/Jr for anonymous and candidate genes whose expression was regulated by dietary sodium. Methods mRNA quantitation of both candidate genes implicated in sodium excretion and anonymous gene products found by differential hybridization in the kidneys of salt-resistant (SR) and salt sensitive (SS) inbred Dahl rats on high and low salt diets for 21 days. Results Differential screening revealed a cDNA clone (H1) that showed increased dietary salt-dependent expression only in SS rats. Sequencing of the H1 cDNA showed it was the Dahl rat homologue to a perchloric acid soluble protein expressed in liver and kidney. Among candidate genes, transcript levels of arginosuccinate synthetase (AS) and arginosuccinate lyase (AL) were higher in SS on low salt diets, and AS mRNA increased in response to a high salt diet in SR. Renal mRNA for the ANP-A and the vasopressin type II receptors did not differ by strain or dietary conditions. Conclusions Three new salt-sensitive genes were detected in the kidneys of inbred Dahl rats. Two genes encode enzymes in the biosynthesis of l-arginine. The upregulation of these genes by dietary salt indicates increased demand and biosynthesis of l-arginine in Dahl SS rats. A third gene encodes a small acid-soluble protein thought to influence the transcription/translation of numerous genes. Further studies will be needed to determine the nature of the association of these genes with salt-sensitivity and blood pressure. © 2004 Lippincott Williams & Wilkins, Inc.