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

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21 Scopus citations

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 - Oct 2010

ASJC Scopus subject areas

  • Nephrology

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    Sun, P., Lin, D. H., Yue, P., Jiang, H., Gotlinger, K. H., Schwartzman, M. L., Falck, J. R., Goli, M., & 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