Regulation of P-450 4A activity in the glomerulus of the rat

Osamu Ito, Richard J. Roman

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

We recently reported that an enzyme of the cytochrome P-450 4A family is expressed in the glomerulus, but there is no evidence that 20- hydroxyeicosatetraenoic acid (20-HETE) can be produced by this tissue. The purpose of present study was to determine whether glomeruli isolated from the kidney of rats can produce 20-HETE and whether the production of this metabolite is regulated by nitric oxide (NO) and dietary salt intake. Isolated glomeruli produced 20-HETE, dihydroxyeicosatrienoic acids, and 12- hydroxyeicosatetraenoic acid (4.13 ± 0.38, 4.20 ± 0.38, and 2.10 ± 0.20 pmol · min-1 · mg protein-1, respectively) when incubated with arachidonic acid (10 μM). The formation of 20-HETE was dependent on the availability of NADPH and the PO2 of the incubation medium. The formation of 20-HETE was inhibited by NO donors in a concentration-dependent manner. The production of 20-HETE was greater in glomeruli isolated from the kidneys of rats fed a low-salt diet than in kidneys of rats fed a high-salt diet (5.67 ± 0.32 vs. 2.83 ± 0.32 pmol · min-1 · mg protein-1). Immunoblot experiments indicated that the expression of P-450 4A protein in glomeruli from the kidneys of rats fed a low-salt diet was sixfold higher than in kidneys of rats fed a high-salt diet. These results indicate that arachidonic acid is primarily metabolized to 20-HETE and dihydroxyeicosatrienoic acids in glomeruli and that glomerular P-450 activity is modulated by NO and dietary salt intake.

Original languageEnglish
Pages (from-to)R1749-R1757
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume276
Issue number6 45-6
DOIs
Publication statusPublished - 1999 Jun

Keywords

  • 12-hydroxyeicosatetraenoic acid
  • 20-hydroxyeicosatetraenoic acid
  • Cytochrome P-450
  • Eicosanoids
  • Epoxyeicosatrienoic acids
  • Hypertension
  • Nitric oxide
  • Renal disease
  • Renal hemodynamics

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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