Effect of aging on renal cytochrome P450-dependent arachidonic acid metabolism in Dahl rats

J Lipid Mediat. 1993 Mar-Apr;6(1-3):369-73.

Abstract

We investigated the age-related changes of renal cytochrome P450-dependent arachidonic acid metabolism in 3-, 5-, 7-, 9-, 11-, 13- and 20-week-old male Dahl salt-sensitive (DS) and -resistant (DR) rats on a low sodium diet (0.3% NaCl). NADPH-dependent arachidonic acid metabolism was separated and measured by a radio-HPLC system. The formation of 19-hydroxyeicosatetraenoic acid (HETE), 20 HETE, 1,20-dioic acid, epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acid (DHET) was age dependent in both DS and DR rats. omega-Hydroxylase (20-HETE and 1,20-dioic acid formation) and (omega-1)-hydroxylase (19-HETE formation) were increased from 3 to 5 weeks age, then decreased with aging in DR rats. Whilst omega/(omega-1)-hydroxylase activities were increased from 3- to 9-week-old rats, they decreased with aging in DS rats. omega/(omega-1)-Hydroxylase activities were higher in 3-5-week-old DR than DS rats. Epoxygenase activities (EETs and DHET formations) were highest in 3-week-old DS and DR rats, and showed no significant differences between two strains of rats at any ages tested. Renal cytochrome P450-dependent arachidonic acid metabolites have a wide and contrasting spectrum of biological and renal effects, and their relative rates of production may influence not only renal hemodynamics but also pro- and antihypertensive mechanisms of hypertension in Dahl rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Arachidonic Acid / metabolism*
  • Cytochrome P-450 CYP2J2
  • Cytochrome P-450 CYP4A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug Resistance
  • Hypertension / etiology
  • Hypertension / metabolism
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • Mixed Function Oxygenases / metabolism
  • Oxygenases / metabolism
  • Rats
  • Sodium Chloride / pharmacology

Substances

  • Arachidonic Acid
  • Sodium Chloride
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Oxygenases
  • Cytochrome P-450 CYP2J2
  • Cytochrome P-450 CYP4A