Effects of angiotensin converting enzyme inhibitors on renal P450 metabolism of arachidonic acid

Osamu Ito, Richard J. Roman, Ken Omata, Kazuhisa Takeuchi, Sadayoshi Ito

Research output: Contribution to journalArticlepeer-review

Abstract

The present study examined the effects of angiotensin converting enzyme (ACE) inhibitors and an angiotensin II type 1 (AT1) receptor antagonist on the metabolism of arachidonic acid (AA) in the kidney. Male Sprague-Dawley rats were treated with vehicle, captopril, enalapril, or candesartan for one week. The production of 20-hydroxy-eicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) by renal microsomes increased in rats treated with captopril and enalapril. In contrast, blockade of the AT1 receptors with candesartan had no effect on the production of these metabolites. Captopril and enalapril increased the expression of P450 4A protein and P450 reductase protein in renal microsomes. The effects of captopril on the renal matabolism of AA were blocked by either HOE-140, a bradykinin type 2 receptor antagonist or LNAME, a nitric oxide (NO) synthase inhibitor. These results suggest that ACE inhibitors increase the expression of P450 4A and P450 reductase proteins in the kidney and enhance the formation of 20-HETE and EETs secondary to increases in intrarenal levels of kinin and NO.

Original languageEnglish
Pages (from-to)1251-1254
Number of pages4
JournalTherapeutic Research
Volume22
Issue number6
Publication statusPublished - 2001

Keywords

  • 20-Hydroxyeicosatetraenoic acid
  • Angiotensin converting enzyme inhibitor
  • Arachidonic acid
  • P450 4A

ASJC Scopus subject areas

  • Medicine(all)

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