Effect of aging on renal cytochrome P450-dependent arachidonic acid metabolism in Dahl rats.
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.
Omata
K
K
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Tsutsumi
E
E
Sheu
H L
HL
Utsumi
Y
Y
Abe
K
K
D000375:Aging / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D000090762:Cytochrome P-450 CYP2J2; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004351:Drug Resistance; D006973:Hypertension / Q000209:etiology / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology
D016718:Arachidonic Acid; D012965:Sodium Chloride; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010105:Oxygenases; D000090762:Cytochrome P-450 CYP2J2; D042926:Cytochrome P-450 CYP4A