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1 Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
2 Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
3 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
4 Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
5 Human Molecular and Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
* To whom correspondence should be addressed. E-mail: Cowley{at}mcw.edu.
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 rat SS/JrHsdMcwi (SS) attenuates the development of salt-sensitive hypertension and renal damage. In order 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-13BN and the SS rat. Blood pressure was determined in chronically catheterized rats after 2 weeks 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 22 to 32 mmHg. Protection was more robust in female than in 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.
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