title: Analyses of differential gene expression in genetic hypertensive rats by microarray.
abstract: 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.
authors.affiliation: Research Institute, National Cardiovascular Center, Suita, Osaka, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Okuda
authors.forename: Toshiki
authors.initials: T
authors.lastname: Sumiya
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Mizutani
authors.forename: Naomi
authors.initials: N
authors.lastname: Tago
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.forename: Tadashi
authors.initials: T
authors.lastname: Tanabe
authors.forename: Hisao
authors.initials: H
authors.lastname: Kato
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Higaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Tsujita
authors.forename: Naoharu
authors.initials: N
authors.lastname: Iwai
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Muzutani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kato
mesh_terms: 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
chemical_list: D000959:Antihypertensive Agents