Exclusion of the catechol-o-methyltransferase gene from genes contributing to salt-sensitive hypertension in dahl salt-sensitive rats.
Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines. Several studies have suggested that this enzyme may play a role in blood pressure regulation. We previously reported that the expression levels of Comt mRNA in Dahl salt-sensitive (DS) rats were lower than those in Lewis (LEW) rats. However, the physiological significance of this phenomenon has not been investigated. The purpose of the present study was to evaluate the significance of lower expression of Comt in Dahl salt-sensitive hypertension. The Comt gene in DS rats has a palindromic insertion in 3'-untranslated region, which appears to be responsible for reduced mRNA stability. A genome-wide quantitative trait loci (QTL) analysis of blood pressure using 107 F2 rats indicated that a statistically significant QTL for pulse pressure was located at the Comt locus in chromosome 11. Microarray analysis confirmed that Comt was the only gene differentially expressed between DS and LEW rats in this chromosomal region. However, COMT inhibitors had no significant effects on blood pressure in either DS or LEW rats. Thus, Comt was excluded from the candidate genes contributing to salt-sensitive hypertension in DS rats. A true gene responsible for pulse pressure in this chromosome 11 region remains to be determined.
Kajimoto
Kazuaki
K
Department of Epidemiology, Research Institute, National Cardiovascular Center, Suita, Japan.
Hiura
Yumiko
Y
Sumiya
Toshiki
T
Yasui
Naomi
N
Okuda
Tomohiko
T
Iwai
Naoharu
N
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D051381:Rats; D020303:Rats, Inbred Dahl; D011917:Rats, Inbred Lew; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
D020413:3' Untranslated Regions; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D002394:Catechol O-Methyltransferase