Exclusion of the catechol-o-methyltransferase gene from genes contributing to salt-sensitive hypertension in dahl salt-sensitive rats

Exclusion of the catechol-o-methyltransferase gene from genes contributing to salt-sensitive hypertension in dahl salt-sensitive rats


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ABSTRACT 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


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access 09 January 2024 ARTICLE PDF REFERENCES * Iwai N, Yasui N, Naraba H, Tago N, Yamawaki H, Sumiya H : Klk1 as one of the genes contributing to hypertension in Dahl salt-sensitive rat.


_Hypertension_ 2005; 45: 947–953. Article  CAS  Google Scholar  * Moujahidine M, Lambert R, Dutil J, _et al_: Combining congenic coverage with gene profiling in search of candidates for


blood pressure quantitative trait loci in Dahl rats. _Hypertens Res_ 2004; 27: 203–212. Article  CAS  Google Scholar  * Garrett MR, Dene H, Walder R, _et al_: Genome scan and congenic


strains for blood pressure QTL using Dahl salt-sensitive rats. _Genome Res_ 1998; 8: 711–723. Article  CAS  Google Scholar  * Okuda T, Sumiya T, Iwai N, Miyata T : Pyridoxine 5′-phosphate


oxidase is a candidate gene responsible for hypertension in Dahl-S rats. _Biochem Biophys Res Commun_ 2004; 313: 647–653. Article  CAS  Google Scholar  * Karhunen T, Tilgmann C, Ulmanen I,


Julkunen I, Panula P : Distribution of catechol-_O_-methyltransferase enzyme in rat tissues. _J Histochem Cytochem_ 1994; 42: 1079–1090. Article  CAS  Google Scholar  * Axelrod J, Albers W,


Clemente CD : Distribution of catechol-_O_-methyltransferase in the nervous system and other tissues. _J Neurochem_ 1959; 5: 68–72. Article  CAS  Google Scholar  * Tsunoda M, Tenhunen J,


Tilgmann C, Arai H, Imai K : Reduced membrane-bound catechol-_O_-methyltransferase in the liver of spontaneously hypertensive rats. _Hypertens Res_ 2003; 26: 923–927. Article  CAS  Google


Scholar  * Masuda M, Tsunoda M, Imai K : Low catechol-_O_-methyltransferase activity in the brain and blood pressure regulation. _Biol Pharm Bull_ 2006; 29: 202–205. Article  CAS  Google


Scholar  * Jordan J, Lipp A, Tank J, _et al_: Catechol-_O_-methyltransferase and blood pressure in humans. _Circulation_ 2002; 106: 460–465. Article  CAS  Google Scholar  * Helkamaa T,


Mannisto PT, Rauhala P, _et al_: Resistance to salt-induced hypertension in catechol-_O_-methyltransferase-gene–disrupted mice. _J Hypertens_ 2003; 21: 2365–2374. Article  CAS  Google


Scholar  * Eklof AC, Holtback U, Sundelof M, Chen S, Aperia A : Inhibition of COMT induces dopamine-dependent natriuresis and inhibition of proximal tubular Na+,K+-ATPase. _Kidney Int_ 1997;


52: 742–747. Article  CAS  Google Scholar  * Hansell P, Odlind C, Mannisto PT : Different renal effects of two inhibitors of catechol-_O_-methylation in the rat: entacapone and CGP 28014.


_Acta Physiol Scand_ 1998; 162: 489–494. Article  CAS  Google Scholar  * Sambrook J, Russell DW : _Molecular Cloning: A Laboratory Manual_, 3rd ed. Cold Spring Harbor Laboratory, Cold Spring


Harbor, 2001, pp 6.4–6.12. Google Scholar  * Nagai R, Nagata S : New algorithmic-based digital filter processing system for real-time continuous blood pressure measurement and analysis in


conscious rats. _Comput Biol Med_ 1995; 25: 483–494. Article  CAS  Google Scholar  * Manly KF, Cudmore RH Jr, Meer JM : Map Manager QTX, cross-platform software for genetic mapping. _Mamm


Genome_ 2001; 12: 930–932. Article  CAS  Google Scholar  * Okuda T, Sumiya T, Mizutani K, _et al_: Analyses of differential gene expression in genetic hypertensive rats by microarray.


_Hypertens Res_ 2002; 25: 249–255. Article  CAS  Google Scholar  * Nissinen E, Linden IB, Schultz E, Kaakkola S, Mannisto PT, Pohto P : Inhibition of catechol-_O_-methyltransferase activity


by two novel disubstituted catechols in the rat. _Eur J Pharmacol_ 1988; 153: 263–269. Article  CAS  Google Scholar  * Harrold S, Genovese C, Kobrin B, Morrison SL, Milcarek C : A comparison


of apparent mRNA half-life using kinetic labeling techniques _vs_ decay following administration of transcriptional inhibitors. _Anal Biochem_ 1991; 198: 19–29. Article  CAS  Google Scholar


  * Inomata H, Watanabe T, Iizuka Y, _et al_: Identification of quantitative trait loci for cardiac hypertrophy in two different strains of the spontaneously hypertensive rat. _Hypertens


Res_ 2005; 28: 273–281. Article  CAS  Google Scholar  * Pearson H : Genetics: what is a gene? _Nature_ 2006; 441: 398–401. Article  CAS  Google Scholar  * Carninci P, Kasukawa T, Katayama S,


_et al_: The transcriptional landscape of the mammalian genome. _Science_ 2005; 309: 1559–1563. Article  CAS  Google Scholar  * Katayama S, Tomaru Y, Kasukawa T, _et al_: Antisense


transcription in the mammalian transcriptome. _Science_ 2005; 309: 1564–1566. Article  Google Scholar  * Akiva P, Toporik A, Edelheit S, _et al_: Transcription-mediated gene fusion in the


human genome. _Genome Res_ 2006; 16: 30–36. Article  CAS  Google Scholar  * Spilianakis CG, Lalioti MD, Town T, Lee GR, Flavell RA : Interchromosomal associations between alternatively


expressed loci. _Nature_ 2005; 435: 637–645. Article  CAS  Google Scholar  Download references AUTHOR INFORMATION Author notes * Kazuaki Kajimoto, Yumiko Hiura and Toshiki Sumiya: These


authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Department of Epidemiology, Research Institute, National Cardiovascular Center, Suita, Japan Kazuaki Kajimoto, Yumiko


Hiura, Toshiki Sumiya, Naomi Yasui, Tomohiko Okuda & Naoharu Iwai Authors * Kazuaki Kajimoto View author publications You can also search for this author inPubMed Google Scholar * Yumiko


Hiura View author publications You can also search for this author inPubMed Google Scholar * Toshiki Sumiya View author publications You can also search for this author inPubMed Google


Scholar * Naomi Yasui View author publications You can also search for this author inPubMed Google Scholar * Tomohiko Okuda View author publications You can also search for this author


inPubMed Google Scholar * Naoharu Iwai View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Naoharu Iwai. RIGHTS AND


PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kajimoto, K., Hiura, Y., Sumiya, T. _et al._ Exclusion of the Catechol-_O_-Methyltransferase Gene from Genes


Contributing to Salt-Sensitive Hypertension in Dahl Salt-Sensitive Rats. _Hypertens Res_ 30, 459–467 (2007). https://doi.org/10.1291/hypres.30.459 Download citation * Received: 20 September


2006 * Accepted: 20 December 2006 * Issue Date: 01 May 2007 * DOI: https://doi.org/10.1291/hypres.30.459 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this


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KEYWORDS * _Comt_ * quantitative trait loci * genetics * hypertension * salt