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1 Pharmacology, New York Medical College, Valhalla, New York, United States
2 C. & M. Physiology, Yale University, New Haven, Connecticut, United States
3 Dept of Pharmacology, New York Medical College, Valhalla, New York, United States
* To whom correspondence should be addressed. E-mail: wenhui_wang{at}nymc.edu.
The cytochrome P450(CYP) epoxygenase-dependent metabolism of arachidonic acid (AA) has been shown to inhibit ENaC. Now we tested the effect of low Na intake on CYP2C23. Immunostaining showed that CYP2C23 is expressed in the TAL and collecting duct (CD). Na restriction significantly suppressed the expression of CYP2C23 in the TAL and CD. Western blot also demonstrated that the expression of CYP2C23 in renal cortex and outer medulla diminished in rats on Na deficient diet (Na-D) but increased in those on high Na diet (4%). Moreover, the content of 11,12 epoxyeicosatrienoic acid (EET) decreased in the isolated CCD from rats on Na-D in comparison to those on a normal Na diet (0.5%). Patch clamp study showed that application of 15 µm AA inhibited the activity of ENaC by 77% in the CCD of rats on a Na-D for three days. However, the inhibitory effect of AA on ENaC was significantly attenuated in rats on Na-D for 14 days. Furthermore, inhibition of CYP epoxygenase with MS-PPOH increased the ENaC activity in the CCD of rats on a control Na diet. We also used microperfusion technique to examine the effect of MS-PPOH on Na transport in the distal nephron. Application of MS-PPOH significantly increased Na absorption in the distal nephron of control rats but had no significant effect on Na absorption in rats on Na-D for 14 days. We conclude that low Na intake downregulates the activity and expression of CYP2C23 and attenuates the inhibitory effect of AA on Na transport.
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