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Articles in PresS, published online ahead of print January 2, 2002
Physiol Genomics, 10.1152/physiolgenomics.00083.2001
Submitted on September 20, 2001
Accepted on December 20, 2001
1 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
* To whom correspondence should be addressed. E-mail: mliang{at}mcw.edu.
Substitution of chromosome 13 from Brown Norway (BN)rats into the Dahl salt-sensitive (SS/Mcw) rats resulted in substantial reduction of blood pressure salt-sensitivity in this consomic rat strain designated SSBN13. In the present study, we attempted to identify genes associated with salt-sensitive hypertension by utilizing a custom, known-gene cDNA microarray to compare the mRNA expression profiles in the renal medulla (a tissue playing a pivotal role in long term blood pressure regulation) of SS/Mcw and SSBN13 rats on either low (0.4% NaCl) or high (4% NaCl, 2 weeks) salt diets. In order to increase the reliability of microarray data, we designed a four-way comparison experiment incorporating several levels of replication and developed a conservative yet robust data analysis method. Using this approach, from the 1,751 genes examined (representing more than 80% of all currently known rat genes), 80 were identified as being differentially expressed in at least one of the four comparisons. Substantial agreements were found between the microarray results and the results predicted on the basis of the four-way comparison as well as the results of Northern blots of 20 randomly selected genes. Analysis of the four-way comparison further indicated that approximately 75% of the 80 differentially expressed genes were likely related to salt-sensitive hypertension. Many of these genes had not previously been recognized to be important in hypertension, while several genes/pathways known to be involved in hypertension were confirmed. These results should provide an informative source for designing future functional studies in salt-sensitive hypertension.
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