Document Detail

Role of cytochrome P450 epoxygenase in regulating renal membrane transport and hypertension.
MedLine Citation:
PMID:  23302865     Owner:  NLM     Status:  MEDLINE    
PURPOSE OF REVIEW: Cytochrome P450 (CYP)-epoxygenase is highly expressed in the kidney and its metabolism of arachidonic acid plays important roles in regulating renal Na transport and in modulating vasoactivity in the kidney. In the past several years, progress has been made not only in characterizing the specific CYP-epoxygenases responsible for the regulation of membrane transport and vasoactivity in the kidney but also in exploring the mechanism by which they regulate renal Na transport and vasodilation of preglomerular arterioles. This review summarizes and updates recent progress in this area of research.
RECENT FINDINGS: CYP-epoxygenase metabolites of arachidonic acid inhibit epithelial Na channel (ENaC) in the cortical collecting duct (CCD), and 11,12-epoxyeicosatrienoic acid (11,12-EET) is mainly responsible for mediating the inhibitory effect on ENaC. Downregulation of CYP2C44 abolishes arachidonic acid mediated inhibition of ENaC and increases ENaC activity. In addition, 11,12-EET stimulates Ca-activated big conductance K channels in the CCD and afferent arterioles smooth muscles. Activation of big conductance K channels by 11,12-EET is responsible for EET-induced vasodilation in preglomerular arterioles. 11,12-EET-induced vasodilation is absent in preglomerular arterioles pretreated with okadaic acid.
SUMMARY: CYP-epoxygenase mediated suppression of renal Na transport is partially achieved by inhibition of ENaC activity in the CCD and CYP2C44-derived EETs are responsible for inhibition of ENaC. Stimulation of serine/threonine protein phosphatase 2A (PP2A) contributes to 11,12-EET-induced activation of big conductance K channels and vasodilation in preglomerular arterioles.
Jorge Capdevila; Wenhui Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current opinion in nephrology and hypertension     Volume:  22     ISSN:  1473-6543     ISO Abbreviation:  Curr. Opin. Nephrol. Hypertens.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-04     Completed Date:  2013-07-26     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9303753     Medline TA:  Curr Opin Nephrol Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  163-9     Citation Subset:  IM    
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MeSH Terms
Arachidonic Acid / metabolism
Blood Pressure
Cytochrome P-450 Enzyme System / genetics,  metabolism*
Epithelial Sodium Channels / drug effects,  metabolism*
Hypertension / enzymology*,  genetics,  physiopathology
Kidney / blood supply,  enzymology*,  physiopathology
Mice, Transgenic
Polymorphism, Genetic
Potassium Channels / metabolism
Signal Transduction
Sodium / metabolism
Grant Support
Reg. No./Substance:
0/Epithelial Sodium Channels; 0/Potassium Channels; 27YG812J1I/Arachidonic Acid; 9035-51-2/Cytochrome P-450 Enzyme System; 9NEZ333N27/Sodium; EC epoxygenase

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