Document Detail


Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion.
MedLine Citation:
PMID:  14718355     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Plasma levels of aldosterone are not always predictable from the activity of renin and the concentration of potassium. Among the unexplained are elevated levels of aldosterone in some obese humans. Obesity is characterized by increased plasma fatty acids and oxidative stress. We postulated that oxidized fatty acids stimulate aldosteronogenesis. The most readily oxidized fatty acids are the polyunsaturated, and the most abundant of those is linoleic acid. We tested oxidized derivatives of linoleic acid for effects on rat adrenal cells. One derivative, 12,13-epoxy-9-keto-10(trans)-octadecenoic acid (EKODE), was particularly potent. EKODE stimulated aldosteronogenesis at concentrations from 0.5 to 5 micromol/L, and inhibited aldosteronogenesis at higher doses. EKODE's stimulatory effect was most prominent when angiotensin and potassium effects were submaximal. The lipid's mechanism of action was on the early pathway leading to pregnenolone; its action was inhibited by atrial natriuretic peptide. Plasma EKODE was measured by liquid chromatography/mass spectrometry. All human plasmas tested contained EKODE in concentrations ranging from 10(-9) to 5x10(-7) mol/L. In samples from 24 adults, levels of EKODE correlated directly with aldosterone (r=0.53, P=0.007). In the 12 blacks in that cohort, EKODE also correlated with body mass index and systolic pressure. Those other correlations were not seen in white subjects. The results suggest that oxidized derivatives of polyunsaturated fatty acids other than arachidonic are biologically active. Compounds like EKODE, derived from linoleic acid, may affect adrenal steroid production in humans and mediate some of the deleterious effects of obesity and oxidative stress, especially in blacks.
Authors:
Theodore L Goodfriend; Dennis L Ball; Brent M Egan; William B Campbell; Kasem Nithipatikom
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2004-01-12
Journal Detail:
Title:  Hypertension     Volume:  43     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-30     Completed Date:  2004-04-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  358-63     Citation Subset:  IM    
Affiliation:
William S. Middleton Memorial Veterans Hospital and Department of Medicine of the University of Wisconsin 53705, USA. theodore.goodfriend@med.va.gov
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MeSH Terms
Descriptor/Qualifier:
Adult
African Continental Ancestry Group
Aldosterone / biosynthesis*,  blood,  secretion
Animals
Cells, Cultured
Humans
Linoleic Acid / chemistry
Middle Aged
Obesity / blood,  ethnology
Oleic Acids / blood,  chemistry,  pharmacology*
Rats
Zona Glomerulosa / cytology,  drug effects,  metabolism
Chemical
Reg. No./Substance:
0/12,13-epoxy-9- keto-10-octadecenoic acid; 0/Oleic Acids; 2197-37-7/Linoleic Acid; 52-39-1/Aldosterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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