Document Detail

Effects of converting enzyme inhibitors on renal P-450 metabolism of arachidonic acid.
MedLine Citation:
PMID:  11171663     Owner:  NLM     Status:  MEDLINE    
The effects of blockade of the renin-angiotensin system on the renal metabolism of arachidonic acid (AA) were examined. Male Sprague-Dawley rats were treated with vehicle, captopril (25 mg x kg(-1) x day(-1)), enalapril (10 mg x kg(-1) x day(-1)), or candesartan (1 mg x kg(-1) x day(-1)) for 1 wk. The production of 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) by renal cortical microsomes increased in rats treated with captopril by 59 and 24% and by 90 and 58% in rats treated with enalapril. Captopril and enalapril increased 20-HETE production in the outer medulla by 100 and 143%, respectively. In contrast, blockade of ANG II type 1 receptors with candesartan had no effect on the renal metabolism of AA. Captopril and enalapril increased cytochrome P-450 (CYP450) reductase protein levels in the renal cortex and outer medulla and the expression of CYP450 4A protein in the outer medulla. The effects of captopril on the renal metabolism of AA were prevented by the bradykinin-receptor antagonist, HOE-140, or the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester. These results suggest that angiotensin-converting enzyme inhibitors may increase the formation of 20-HETE and EETs secondary to increases in the intrarenal levels of kinins and NO.
O Ito; K Omata; S Ito; K M Hoagland; R J Roman
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  280     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-03-22     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R822-30     Citation Subset:  IM    
Department of Nephrology, Endocrinology, and Hypertension, Tohoku University Graduate School of Medicine, Sendai 980 - 8574, Japan.
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MeSH Terms
8,11,14-Eicosatrienoic Acid / metabolism
Alkane 1-Monooxygenase
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Arachidonic Acid / metabolism*
Benzimidazoles / pharmacology
Bradykinin / analogs & derivatives*,  pharmacology
Captopril / pharmacology
Cytochrome P-450 Enzyme System / metabolism*
Desoxycorticosterone / pharmacology
Enalapril / pharmacology
Enzyme Inhibitors / pharmacology
Hydroxyeicosatetraenoic Acids / metabolism
Kidney / enzymology*
Kidney Cortex / ultrastructure
Kidney Medulla / ultrastructure
Microsomes / enzymology
Mixed Function Oxygenases / metabolism
NADPH-Ferrihemoprotein Reductase / metabolism
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase / antagonists & inhibitors
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Bradykinin / antagonists & inhibitors
Spironolactone / pharmacology
Tetrazoles / pharmacology
Grant Support
Reg. No./Substance:
0/Angiotensin Receptor Antagonists; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Benzimidazoles; 0/Enzyme Inhibitors; 0/Hydroxyeicosatetraenoic Acids; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Receptors, Bradykinin; 0/Tetrazoles; 506-32-1/Arachidonic Acid; 50903-99-6/NG-Nitroarginine Methyl Ester; 52-01-7/Spironolactone; 58-82-2/Bradykinin; 62571-86-2/Captopril; 64-85-7/Desoxycorticosterone; 7324-41-6/8,11,14-Eicosatrienoic Acid; 75847-73-3/Enalapril; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; 7PG89G35Q7/icatibant; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Mixed Function Oxygenases; EC Oxide Synthase; EC 1-Monooxygenase; EC Reductase; S8Q36MD2XX/candesartan

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