Induction of renal cytochrome P450 arachidonic acid epoxygenase activity by dietary gamma-linolenic acid.
Dietary gamma-linolenic acid (GLA), a omega-6 polyunsaturated fatty acid found in borage oil (BOR), lowers systolic blood pressure in spontaneously hypertensive rats (SHRs). GLA is converted into arachidonic acid (AA) by elongation and desaturation steps. Epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are cytochrome P450 (P450)-derived AA eicosanoids with important roles in regulating blood pressure. This study tested the hypothesis that the blood pressure-lowering effect of a GLA-enriched diet involves alteration of P450-catalyzed AA metabolism. Microsomes and RNA were isolated from the renal cortex of male SHRs fed a basal fat-free diet for 5 weeks to which 11% by weight of sesame oil (SES) or BOR was added. There was a 2.6- to 3.5-fold increase in P450 epoxygenase activity in renal microsomes isolated from the BOR-fed SHRs compared with the SES-fed rats. Epoxygenase activity accounted for 58% of the total AA metabolism in the BOR-treated kidney microsomes compared with 33% in the SES-treated rats. More importantly, renal 14,15- and 8,9-EET levels increased 1.6- to 2.5-fold after dietary BOR treatment. The increase in EET formation is consistent with increases in CYP2C23, CYP2C11, and CYP2J protein levels. There were no differences in the level of renal P450 epoxygenase mRNA between the SES- and BOR-treated rats. Enhanced synthesis of the vasodilatory EETs and decreased formation of the vasoconstrictive 20-HETE suggests that changes in P450-mediated AA metabolism may contribute, at least in part, to the blood pressure-lowering effect of a BOR-enriched diet.
Yu
Zhigang
Z
Department of Biopharmaceutical Sciences, University of California San Francisco, San Francisco, CA 94143, USA.
Ng
Valerie Y
VY
Su
Ping
P
Engler
Marguerite M
MM
Engler
Mary B
MB
Huang
Yong
Y
Lin
Emil
E
Kroetz
Deanna L
DL
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D015153:Blotting, Western; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004041:Dietary Fats / Q000008:administration & dosage*; D004790:Enzyme Induction; D006973:Hypertension / Q000178:diet therapy*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010105:Oxygenases / Q000096:biosynthesis*; D051381:Rats; D011918:Rats, Inbred SHR; D017965:gamma-Linolenic Acid / Q000008:administration & dosage*
D001095:Arachidonic Acids; C000717351:Cyp2c23 protein, rat; D004041:Dietary Fats; D017965:gamma-Linolenic Acid; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000090762:Cytochrome P-450 CYP2J2