Gender differences of renal CYP-derived eicosanoid synthesis in rats fed a high-fat diet.
BACKGROUND
Renal cytochrome P450 (CYP)-derived eicosanoids, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs), have been shown to affect renal function and blood pressure (BP). We recently reported that high fat (HF) diet treatment in male rats increases BP and decreases production of these eicosanoids in the kidneys. However, at what level the downregulation of renal eicosanoid synthesis occurs and whether the HF diet has any effects on the regulation of renal eicosanoid synthesis in female rats are not known. The purpose of this study was to determine renal CYP-derived eicosanoid synthesis and its association with BP regulation in HF male and female rats.


METHODS
In the first set of experiments, male and female rats were fed the HF or control diet for 10 weeks. In the second set of experiments, male and female rats were fed the HF diet for 10 days. In the third set of experiments, HF-fed and control female rats were treated with 5alpha-dihydrotestosterone for 4 weeks. After treatment, BP, urinary sodium, sodium balance, eicosanoid production, and CYP enzyme expression were determined.


RESULTS
An elevation of BP and a decrease of renal cortical eicosanoid production were found in HF male rats, but no BP and eicosanoid production changes were observed in HF female rats. The HF treatment also caused a significant decrease of eicosanoid production and a decrease of CYP4A and 2C23 expression in the proximal tubules of HF male rats. Moreover, the HF diet treatment in male rats caused an increase in cumulative sodium balance and an elevation of BP, whereas no change in cumulative sodium balance and BP was observed in female rats. The treatment of 5alpha-dihydrotestosterone increased BP and 20-HETE production in the renal microvessels, but had no effect on urinary sodium excretion and renal microvessel EET production in both control and HF-fed female rats.


CONCLUSIONS
These results demonstrate that there are gender-specific differences in regulation of renal eicosanoid synthesis, sodium balance, and BP caused by HF treatment, and it appears that androgens play some role in upregulation of renal microvessel 20-HETE production in both HF and control female rats.
Zhou
Yiqiang
Y
Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Lin
Songbai
S
Chang
Hsin-Hsin
HH
Du
Juan
J
Dong
Zheng
Z
Dorrance
Anne M
AM
Brands
Michael W
MW
Wang
Mong-Heng
MH
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D000090762:Cytochrome P-450 CYP2J2; D042926:Cytochrome P-450 CYP4A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000096:biosynthesis*; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D012964:Sodium / Q000378:metabolism
D000728:Androgens; D004041:Dietary Fats; D015777:Eicosanoids; D013196:Dihydrotestosterone; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D012964:Sodium; D000090762:Cytochrome P-450 CYP2J2; D042926:Cytochrome P-450 CYP4A