Induction of Renal Cytochrome P450 Arachidonic Acid Epoxygenase Activity by {gamma}-Linolenic Acid


Yu Z, Ng VY, Su P, Engler MM, Engler MB, Huang Y et al. J Pharmacol Exp Ther 2006;317:732-38.


Dietary {gamma}-linolenic acid (GLA), an {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 (CYP) 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 CYP-catalyzed AA metabolism. Microsomes and RNA were isolated from the renal cortex of male SHRs fed a basal fat-free diet for 5 wks to which 11% by weight of sesame oil (SES) or BOR was added. There was a 2.6- to 3.5-fold increase in CYP epoxygenase activity in renal microsomes isolated from the BOR fed SHRs compared to the SES fed rats. Epoxygenase activity accounted for 58% of the total AA metabolism in the BOR treated kidney microsomes compared to 33% in the SES treated rats. More importantly, renal 14,15- and 8,9-EET levels increased 1.6- to 2.5-fold following 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 CYP 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 CYP-mediated AA metabolism may contribute, at least in part, to the blood pressure lowering effect of a BOR-enriched diet.