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High K intake enhanced the inhibition of ENaC induced by arachidonic acid (AA).
Author(s) -
Sun Peng,
Jin Yan,
Wang WenHui
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1337-d
Subject(s) - epoxygenase , epithelial sodium channel , endocrinology , medicine , arachidonic acid , chemistry , cytochrome p450 , aldosterone , sodium , biology , biochemistry , metabolism , enzyme , organic chemistry
We previously demonstrated that AA inhibited ENaC in the CCD and that the effect of AA was mediated by the cytochrome 450 (CYP) epoxygenase‐dependent metabolic pathway because 11,12‐EET mimicked the effect of AA on ENaC (JGP, 124:, 2004). In the present study, we examined the effect of AA on ENaC in the CCD from rats on a high K diet (HK). Application of AA inhibited ENaC and the effect of AA was abolished by MS‐PPOH, an inhibitor of CYP epoxygenase. The dose response curve of the AA effect on ENaC shows that the sensitivity of ENaC to AA in the CCD from rats on HK is shifted to the left in comparison to those on a low Na diet for 3 days. In contrast, the dose response curve of the AA effect in the CCD from rats on a low Na intake for 14 days was significantly shifted to the right. Western blot further shows that HK intake significantly increased while a low Na intake decreased the expression of CYP2C23 in the renal cortex and outer medulla. The possibility that increased sensitivity of ENaC to AA is due to a high expression of CYP epoxygenase is also confirmed by observation that the sensitivity of ENaC to 11,12‐EET was the same among the three groups. We conclude that increased expression of CYP epoxygenase is responsible for the enhanced AA sensitivity of ENaC and that aldosterone is not responsible for mediating the stimulatory effect of HK on the expression of CYP2C23 because low Na intake, which increases aldosterone levels, did not mimic the effect of HK and suppressed the expression of CYP2C23.