High potassium intake enhances the inhibitory effect of 11,12-EET on ENaC

Peng Sun, Dao Hong Lin, Peng Yue, Houli Jiang, Katherine H. Gotlinger, Michal L. Schwartzman, J R Falck, Mohan Goli, Wen Hui Wang

Research output: Contribution to journalArticle

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Abstract

High dietary potassium stimulates the renal expression of cytochrome P450 (CYP) epoxygenase 2C23, which metabolizes arachidonic acid (AA). Because the AA metabolite 11,12-epoxyeicosatrienoic acid (11,12-EET) can inhibit the epithelial sodium channel (ENaC) in the cortical collecting duct, we tested whether dietary potassium modulates ENaC function. High dietary potassium increased 11,12-EET in the isolated cortical collecting duct, an effect mimicked by inhibiting the angiotensin II type I receptor with valsartan. In patch-clamp experiments, a high potassium intake or treatment with valsartan enhanced AA-induced inhibition of ENaC, an effect mediated by a CYP-epoxygenase-dependent pathway. Moreover, high dietary potassium and valsartan each augmented the inhibitory effect of 11,12-EET on ENaC. Liquid chromatography/mass spectrometry showed that the rate of EET conversion to dihydroxyeicosatrienoic acids (DHET) was lower in renal tissue obtained from rats on a high-potassium diet than from those on a control diet, but this was not a result of altered expression of soluble epoxide hydrolase (sEH). Instead, suppression of sEH activity seemed to be responsible for the 11,12-EET-mediated enhanced inhibition of ENaC in animals on a high-potassium diet. Patch-clamp experiments demonstrated that 11,12-DHET was a weak inhibitor of ENaC compared with 11,12-EET, whereas 8,9- and 14,15-DHET were not. Furthermore, inhibition of sEH enhanced the 11,12-EET-induced inhibition of ENaC similar to high dietary potassium. In conclusion, high dietary potassium enhances the inhibitory effect of AA and 11,12-EET on ENaC by increasing CYP epoxygenase activity and decreasing sEH activity, respectively.

Original languageEnglish (US)
Pages (from-to)1667-1677
Number of pages11
JournalJournal of the American Society of Nephrology
Volume21
Issue number10
DOIs
StatePublished - 2010

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Dietary Potassium
Valsartan
Potassium
Epoxide Hydrolases
Arachidonic Acid
Cytochrome P-450 Enzyme System
Diet
Epithelial Sodium Channels
Kidney
Angiotensin I
Angiotensin Receptors
11,12-epoxy-5,8,14-eicosatrienoic acid
Liquid Chromatography
Mass Spectrometry
Acids

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Cite this

Sun, P., Lin, D. H., Yue, P., Jiang, H., Gotlinger, K. H., Schwartzman, M. L., ... Wang, W. H. (2010). High potassium intake enhances the inhibitory effect of 11,12-EET on ENaC. Journal of the American Society of Nephrology, 21(10), 1667-1677. https://doi.org/10.1681/ASN.2009111110

High potassium intake enhances the inhibitory effect of 11,12-EET on ENaC. / Sun, Peng; Lin, Dao Hong; Yue, Peng; Jiang, Houli; Gotlinger, Katherine H.; Schwartzman, Michal L.; Falck, J R; Goli, Mohan; Wang, Wen Hui.

In: Journal of the American Society of Nephrology, Vol. 21, No. 10, 2010, p. 1667-1677.

Research output: Contribution to journalArticle

Sun, P, Lin, DH, Yue, P, Jiang, H, Gotlinger, KH, Schwartzman, ML, Falck, JR, Goli, M & Wang, WH 2010, 'High potassium intake enhances the inhibitory effect of 11,12-EET on ENaC', Journal of the American Society of Nephrology, vol. 21, no. 10, pp. 1667-1677. https://doi.org/10.1681/ASN.2009111110
Sun, Peng ; Lin, Dao Hong ; Yue, Peng ; Jiang, Houli ; Gotlinger, Katherine H. ; Schwartzman, Michal L. ; Falck, J R ; Goli, Mohan ; Wang, Wen Hui. / High potassium intake enhances the inhibitory effect of 11,12-EET on ENaC. In: Journal of the American Society of Nephrology. 2010 ; Vol. 21, No. 10. pp. 1667-1677.
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abstract = "High dietary potassium stimulates the renal expression of cytochrome P450 (CYP) epoxygenase 2C23, which metabolizes arachidonic acid (AA). Because the AA metabolite 11,12-epoxyeicosatrienoic acid (11,12-EET) can inhibit the epithelial sodium channel (ENaC) in the cortical collecting duct, we tested whether dietary potassium modulates ENaC function. High dietary potassium increased 11,12-EET in the isolated cortical collecting duct, an effect mimicked by inhibiting the angiotensin II type I receptor with valsartan. In patch-clamp experiments, a high potassium intake or treatment with valsartan enhanced AA-induced inhibition of ENaC, an effect mediated by a CYP-epoxygenase-dependent pathway. Moreover, high dietary potassium and valsartan each augmented the inhibitory effect of 11,12-EET on ENaC. Liquid chromatography/mass spectrometry showed that the rate of EET conversion to dihydroxyeicosatrienoic acids (DHET) was lower in renal tissue obtained from rats on a high-potassium diet than from those on a control diet, but this was not a result of altered expression of soluble epoxide hydrolase (sEH). Instead, suppression of sEH activity seemed to be responsible for the 11,12-EET-mediated enhanced inhibition of ENaC in animals on a high-potassium diet. Patch-clamp experiments demonstrated that 11,12-DHET was a weak inhibitor of ENaC compared with 11,12-EET, whereas 8,9- and 14,15-DHET were not. Furthermore, inhibition of sEH enhanced the 11,12-EET-induced inhibition of ENaC similar to high dietary potassium. In conclusion, high dietary potassium enhances the inhibitory effect of AA and 11,12-EET on ENaC by increasing CYP epoxygenase activity and decreasing sEH activity, respectively.",
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AU - Goli, Mohan

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