Document Detail

Renal P450 metabolites of arachidonic acid and the development of hypertension in Dahl salt-sensitive rats.
MedLine Citation:
PMID:  9160783     Owner:  NLM     Status:  MEDLINE    
Renal transplantation studies indicate that some form of renal dysfunction underlies the development of hypertension in Dahl salt-sensitive (S) rats; however, the factors responsible for altering kidney function remain to be determined. Previous studies have indicated that Dahl S rats require a higher renal perfusion pressure to excrete the same amount of sodium and water as normotensive rats and that this is due largely to an elevation in Cl- transport in the thick ascending limb of the loop of Henle. There are now five lines of evidence that suggest an abnormality in the renal metabolism of arachidonic acid by enzymes of the P4504A family may contribute to the increase in loop Cl- transport and the development of hypertension in Dahl S rats. In this regard, the formation of 20-HETE and the levels of P4504A protein are reduced in the outer medulla of Dahl S rats. Perfusion of the loop of Henle of Dahl S rats with exogenous 20-HETE normalizes the elevated loop Cl- transport. In addition, a genetic marker in the P4504A2 gene, which encodes for the enzyme that makes 20-HETE, cosegregates with the development of hypertension in an F2 cross of Dahl S and Lewis rats. Finally, induction of renal production of 20-HETE with clofibrate prevents the development of hypertension in Dahl S rats and inhibition of renal 20-HETE formation produces hypertension in Lewis rats fed a high salt diet. These results implicate the CYP4A2 locus as a candidate gene that contributes to the alterations in renal function and the development of hypertension in Dahl S rats.
R J Roman; M Alonso-Galicia; T W Wilson
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  American journal of hypertension     Volume:  10     ISSN:  0895-7061     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-07-17     Completed Date:  1997-07-17     Revised Date:  2009-02-24    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  63S-67S     Citation Subset:  IM    
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
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MeSH Terms
Arachidonic Acid / metabolism
Cytochrome P-450 Enzyme System / metabolism
Drug Resistance / genetics
Hydroxyeicosatetraenoic Acids / physiology*
Hypertension / chemically induced*,  genetics*
Kidney / metabolism*
Rats, Inbred Strains / genetics*
Sodium Chloride*
Reg. No./Substance:
0/Hydroxyeicosatetraenoic Acids; 506-32-1/Arachidonic Acid; 7647-14-5/Sodium Chloride; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; 9035-51-2/Cytochrome P-450 Enzyme System

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