Downregulation of renal CYP-derived eicosanoid synthesis in rats with diet-induced hypertension

Mong Heng Wang, Anita Smith, Yiqiang Zhou, Hsin Hsin Chang, Songbai Lin, Xueying Zhao, John D. Imig, Anne M. Dorrance

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The incidence of essential hypertension increases with obesity; however, the mechanisms that link obesity with hypertension are unclear. Renal cytochrome P450 (CYP)-derived eicosanoids-hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs)-have been shown to play an important role in the regulation of renal function, vascular tone, and blood pressure. The objective of this study was to examine CYP-derived eicosanoid synthesis in the different renal zones (cortex, medulla, and papilla) of rats fed a high fat diet (HF). Male Sprague-Dawley rats were fed a HF diet or regular rat chow for 10 weeks. After 10 weeks, HF rats showed significantly higher systolic blood pressure, body weight, and fat:body weight ratio. The renal ω-hydroxylase activity was decreased by 46% in cortex, 43% in medulla, and 46% in papilla of HF rats. The renal epoxygenase activity was decreased by 46% in cortex, 31% in medulla, and 56% in papilla of HF rats. Interestingly, the changes in the rate of 20-HETE and EET formation in different renal zones were consistent with the levels of expression of CYP4A and CYP2C23 proteins, respectively. Furthermore, there were no significant changes in the synthesis of these metabolites in the renal microvessels. These results demonstrate that HF diet causes the downregulation of CYP4A and CYP2C23 in renal tubules, and these proteins are responsible for renal 20-HETE and EET formation. The reduction in the synthesis of these eicosanoids may play an important role in the regulation of renal function and blood pressure in obesity-induced hypertension.

Original languageEnglish (US)
Pages (from-to)594-599
Number of pages6
JournalHypertension
Volume42
Issue number4 I
DOIs
StatePublished - Oct 1 2003

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Eicosanoids
Cytochrome P-450 Enzyme System
Down-Regulation
Diet
Hypertension
Kidney
High Fat Diet
Hydroxyeicosatetraenoic Acids
Cytochrome P-450 CYP4A
Acids
Obesity
Blood Pressure
Body Weight
Fat Body
Mixed Function Oxygenases
Microvessels
Blood Vessels
Sprague Dawley Rats
Adipose Tissue
Proteins

Keywords

  • Arachidonic acids
  • Blood pressure
  • Hypertension, obesity
  • Ions
  • Kidney
  • Obesity

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Downregulation of renal CYP-derived eicosanoid synthesis in rats with diet-induced hypertension. / Wang, Mong Heng; Smith, Anita; Zhou, Yiqiang; Chang, Hsin Hsin; Lin, Songbai; Zhao, Xueying; Imig, John D.; Dorrance, Anne M.

In: Hypertension, Vol. 42, No. 4 I, 01.10.2003, p. 594-599.

Research output: Contribution to journalArticle

Wang, MH, Smith, A, Zhou, Y, Chang, HH, Lin, S, Zhao, X, Imig, JD & Dorrance, AM 2003, 'Downregulation of renal CYP-derived eicosanoid synthesis in rats with diet-induced hypertension', Hypertension, vol. 42, no. 4 I, pp. 594-599. https://doi.org/10.1161/01.HYP.0000090123.55365.BA
Wang, Mong Heng ; Smith, Anita ; Zhou, Yiqiang ; Chang, Hsin Hsin ; Lin, Songbai ; Zhao, Xueying ; Imig, John D. ; Dorrance, Anne M. / Downregulation of renal CYP-derived eicosanoid synthesis in rats with diet-induced hypertension. In: Hypertension. 2003 ; Vol. 42, No. 4 I. pp. 594-599.
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AU - Chang, Hsin Hsin

AU - Lin, Songbai

AU - Zhao, Xueying

AU - Imig, John D.

AU - Dorrance, Anne M.

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