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Multiple blood pressure loci on rat chromosome 13 attenuate development of hypertension in the Dahl S hypertensive rat. Physiol Genomics 2007 Oct 22;31(2):228-35

Date

06/15/2007

Pubmed ID

17566075

DOI

10.1152/physiolgenomics.00280.2006

Scopus ID

2-s2.0-35548972551 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

Previous studies have indicated that substitution of chromosome 13 of the salt-resistant Brown Norway BN/SsNHsdMcwi (BN) rat into the genomic background of the Dahl salt-sensitive SS/JrHsdMcwi (SS) rat attenuates the development of salt-sensitive hypertension and renal damage. To identify the regions within chromosome 13 that attenuate the development of hypertension during a high-salt diet in the SS rat, we phenotyped a series of overlapping congenic lines covering chromosome 13, generated from an intercross between the consomic SS-13(BN) rat and the SS rat. Blood pressure was determined in chronically catheterized rats after 2 wk of high-salt diet (8% NaCl) together with microalbuminuria as an index of renal damage. Four discrete regions were identified, ranging in size from 4.5 to 16 Mbp, each of which independently provided significant protection from hypertension during high-salt diet, reducing blood pressure by 20-29 mmHg. Protection was more robust in female than male rats in some of the congenic strains, suggesting a sex interaction with some of the genes determining blood pressure during high-salt diet. Among the 23 congenic strains, several regions overlapped. When three of the "protective" regions were combined onto one broad congenic strain, no summation effect was seen, obtaining the same decrease in blood pressure as with each one independently. We conclude from these studies that there are four regions within chromosome 13 containing genes that interact epistatically and influence arterial pressure.

Author List

Moreno C, Kaldunski ML, Wang T, Roman RJ, Greene AS, Lazar J, Jacob HJ, Cowley AW Jr

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin




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

Albuminuria
Animals
Animals, Congenic
Blood Pressure
Chromosome Mapping
Epistasis, Genetic
Female
Genotype
Hypertension
Male
Phenotype
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Sex Characteristics
Sodium Chloride, Dietary