Renal medullary genes in salt-sensitive hypertension: a chromosomal substitution and cDNA microarray study.
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.
Liang
Mingyu
M
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. mliang@mcw.edu).
Yuan
Baozhi
B
Rute
Elizabeth
E
Greene
Andrew S
AS
Zou
Ai-Ping
AP
Soares
Paulo
P
MCQuestion
Gregory D
GD
Slocum
Glenn R
GR
Jacob
Howard J
HJ
Cowley
Allen W
AW
D000818:Animals; D002875:Chromosomes / Q000235:genetics; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000032:analysis*; D004032:Diet; D020869:Gene Expression Profiling; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D007679:Kidney Medulla / Q000737:chemistry* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D012965:Sodium Chloride / Q000378:metabolism*; D012982:Sodium, Dietary / Q000378:metabolism
D018076:DNA, Complementary; D012982:Sodium, Dietary; D012965:Sodium Chloride