Analyses of differential gene expression in genetic hypertensive rats by microarray.
We identified genes that were differentially expressed between spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) using cDNA microarray analysis, and analyzed the correlation between these genes and hypertension. Twenty four genes were found to be up-regulated and 20 were down-regulated in SHR. We selected 11 genes (6 up-regulated genes: SAH, Hsp70, MCT1, RBP, IDI1, Prion; and 5 down-regulated genes: Thrombin, Dyn, SOD3, Ela1, Gst Y(b)) and subjected them to an F2 cosegregation analysis. One hundred five F2 rats were obtained from the same strains used for microarray analysis, and blood pressure was measured directly with a catheter implanted in the femoral artery. The genotypes of monocarboxylate transporter 1 and glutathione S-transferase Y(b) subunit significantly affected diastolic blood pressure in F2 rats, and these two genes are located near each other on chromosome 2. However, quantitative trait loci (QTL) analysis in this region revealed that the QTL for diastolic blood pressure were from these two genes. Antihypertensive treatment with either enalapril or hydralazine only affected the expression level of Hsp70, which was up-regulated by hydralazine, probably through compensatory sympathetic activation. We were unable to associate the other 10 genes with hypertension in SHR. Based on these results, the identification of differentially expressed genes may not be an efficient method for selecting candidate genes for hypertension in the SHR-WKY system.
Okuda
Tomohiko
T
Research Institute, National Cardiovascular Center, Suita, Osaka, Japan.
Sumiya
Toshiki
T
Mizutani
Ken-ichi
K
Tago
Naomi
N
Miyata
Toshiyuki
T
Tanabe
Tadashi
T
Kato
Hisao
H
Katsuya
Tomohiro
T
Higaki
Jitsuo
J
Ogihara
Toshio
T
Tsujita
Yasuyuki
Y
Iwai
Naoharu
N
Muzutani
Ken-ichi
K
Kato
Hiroshi
H
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002874:Chromosome Mapping; D015870:Gene Expression; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents