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Genetically defined risk of salt sensitivity in an intercross of Brown Norway and Dahl S rats. Physiol Genomics 2000 Apr 27;2(3):107-15 PMID: 11015589

Abstract

A genetic segregation analysis was performed to identify genes that cosegregate with arterial blood pressure traits reflective of salt sensitivity. A population of 113 F2 male rats was derived from an intercross of inbred SS/JrHsd/Mcw (Dahl salt-sensitive) and BN/SsN/Mcw (Brown Norway) rats. Rats were maintained on an 8% salt diet from the age of 9 to 13 wk, and arterial pressure was measured for 3 h daily during the 4th wk of high salt intake in unanesthetized rats using implanted arterial catheters. At the end of the 3rd day of high-salt pressure recordings, the arterial pressure response to salt depletion was determined 1.5 days following treatment with Lasix and a low-sodium (0. 4%) diet. A genome-wide scan using 265 polymorphic simple sequence length polymorphism (SSLP) markers found that seven arterial pressure phenotypes determined at different times and circumstances, and representing two distinct indexes of salt sensitivity, mapped to the same region of rat chromosome 18. The trait of salt sensitivity was strongly influenced by the presence of SS alleles in this region of chromosome 18, and those rats which were homozygote SS/SS exhibited a significantly greater reduction of mean arterial pressure following sodium depletion (29 +/- 2 mmHg) than homozygote BN/BN (17 +/- 3 mmHg) or heterozygotic (22 +/- 2 mmHg) rats. This region of rat chromosome 18 corresponds to the long arm of human chromosome 5 and a region of human chromosome 18 that has been linked to hypertension in humans. Given the unlikely chance of these different blood pressure traits mapping to the same region, we believe these data provide evidence that this region of rat chromosome 18 plays an important role in salt-induced hypertension.

Author List

Cowley AW Jr, Stoll M, Greene AS, Kaldunski ML, Roman RJ, Tonellato PJ, Schork NJ, Dumas P, Jacob HJ

Authors

Allen W. Cowley Jr PhD Chair, Professor in the Physiology department at Medical College of Wisconsin
Andrew S. Greene PhD Interim Vice Chair, Chief, Professor in the Biomedical Engineering department at Medical College of Wisconsin
Peter Tonellato PhD Professor in the School of Public Health department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Alleles
Animals
Blood Pressure
Crosses, Genetic
Diet, Sodium-Restricted
Furosemide
Gene Expression Profiling
Genetic Markers
Genetic Predisposition to Disease
Heterozygote
Homozygote
Hypertension
Linkage (Genetics)
Male
Physical Chromosome Mapping
Quantitative Trait, Heritable
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Sodium Chloride, Dietary



View this publication's entry at the Pubmed website PMID: 11015589
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