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Renal medullary genes in salt-sensitive hypertension: a chromosomal substitution and cDNA microarray study. Physiol Genomics 2002 Feb 28;8(2):139-49

Date

03/05/2002

Pubmed ID

11875192

DOI

10.1152/physiolgenomics.00083.2001

Scopus ID

2-s2.0-0037186992   47 Citations

Abstract

Substitution of chromosome 13 from Brown Norway BN/SsNHsd/Mcw (BN/Mcw) rats into the Dahl salt-sensitive SS/JrHsd/Mcw (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-salt (0.4% NaCl) or high-salt (4% NaCl, 2 wk) diets. 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), we identified 80 as being differentially expressed in at least 1 of the 4 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, whereas 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.

Author List

Liang M, Yuan B, Rute E, Greene AS, Zou AP, Soares P, MCQuestion GD, Slocum GR, Jacob HJ, Cowley AW Jr

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Mingyu Liang PhD Center Director, Professor in the Physiology department at Medical College of Wisconsin




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

Animals
Chromosomes
Crosses, Genetic
DNA, Complementary
Diet
Gene Expression Profiling
Hypertension
Kidney Medulla
Oligonucleotide Array Sequence Analysis
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Sodium Chloride
Sodium, Dietary