Polymorphism in soluble epoxide hydrolase and blood pressure in spontaneously hypertensive rats.

 
TitlePolymorphism in soluble epoxide hydrolase and blood pressure in spontaneously hypertensive rats.
Publication TypeJournal Article
Year of Publication2002
AuthorsFornage, M, Hinojos, CA, Nurowska, BW, Boerwinkle, E, Hammock, BD, Morisseau, CHP, Doris, PA
JournalHypertension
Volume40
Issue4
Pagination485-90
Date Published2002 Oct
ISSN1524-4563
KeywordsAnimals, Blood Pressure, Epoxide Hydrolases, Hypertension, Kidney, Male, Polymorphism, Single Nucleotide, Rats, Rats, Inbred SHR, Rats, Inbred WKY, RNA, Messenger
Abstract

We measured soluble epoxide hydrolase (sEH) renal gene expression in prehypertensive (4 to 5 weeks old) spontaneously hypertensive rats of the Heidelberg SP substrain (SHR [Heid]) and when blood pressure levels entered the hypertensive plateau (17 to 18 weeks old) and compared expression with matched Wistar-Kyoto (WKY [Heid]) rats. Less expression of the gene encoding sEH (EPHX2) was observed in SHR (Heid) than in WKY (Heid). Analysis of sEH protein abundance showed a similar difference. However, no correlation between sEH abundance and blood pressure was observed in the F(2) progeny of a parental strain cross. Measurement of protein abundance in SHR and WKY obtained from Charles River confirmed a recent report that abundance of sEH was greater in SHR (CRiv) than WKY (CRiv) strains. Polymorphisms were detected in EPHX2. Resequencing revealed that 2 alleles of EPHX2 exist in these 4 rat strains, differing by 4 single nucleotide polymorphisms, of which 3 produce nonsynonymous amino acid substitutions. The ancestral allele was shared by SHR (Heid) and WKY (CRiv), and the variant allele was shared by WKY (Heid) and SHR (CRiv). Activity of sEH was greater in animals carrying the variant allele. However, inheritance of this allele was not correlated with blood pressure in the F(2) progeny of a cross between SHR (Heid) and WKY (Heid). These data indicate that sequence variation determining functional alterations in EPHX2 is not likely to contribute to blood pressure levels in SHR.

Alternate JournalHypertension
PubMed ID12364351
Grant ListES05707 / ES / NIEHS NIH HHS / United States
HL69126 / HL / NHLBI NIH HHS / United States
NS41466 / NS / NINDS NIH HHS / United States
P42 ES04699 / ES / NIEHS NIH HHS / United States
R01-DDK45538 / DK / NIDDK NIH HHS / United States
R01-ES02710 / ES / NIEHS NIH HHS / United States