Role of androgens in the renal production of 20-hydroxyeicosatetraenoic acid in spontaneously hypertensive rats

The role of androgens in the production of 20-hydroxyeicosatetraenoic acid (20-HETE) was determined in the kidney of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The renal production of 20-HETE and blood pressure were higher in males than in females at 9 weeks of age. The renal...

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Published inNihon Jinzo Gakkai shi Vol. 46; no. 7; pp. 685 - 692
Main Authors ISHIZUKA, Tsuneo, ITO, Osamu, OMATA, Ken, ITO, Sadayoshi
Format Journal Article
LanguageJapanese
Published Japan Japanese Society of Nephrology 2004
Subjects
20-hydroxyeicosatetraenoic acid
androgen
Androgens - physiology
Animals
cytochrome P-450 4A
Cytochrome P-450 CYP4A - metabolism
Female
gender
Hydroxyeicosatetraenoic Acids - biosynthesis
Hypertension - metabolism
Kidney - metabolism
Male
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Sex Factors
spontaneously hypertensive rats
Testosterone - blood
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Summary:The role of androgens in the production of 20-hydroxyeicosatetraenoic acid (20-HETE) was determined in the kidney of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The renal production of 20-HETE and blood pressure were higher in males than in females at 9 weeks of age. The renal production of 20-HETE was significantly greater in male SHR than in male WKY, whereas it was significantly lower in female SHR than in female WKY. The differences in the renal production of 20-HETE were consistent with the cytochrome P-450 4A protein levels. Plasma free-testosterone levels in male SHR were twice as high as those in male WKY. Castration and treatment with the androgen receptor antagonist, flutamide, reduced blood pressure, the renal production of 20-HETE, and P-450 4A protein levels in both strains. The renal production of 20-HETE was significantly lower in castrated SHR than in castrated WKY. These results indicate that the renal production of 20-HETE and the expression of P-450 4A have gender and strain-differences, and high levels of plasma androgens induce the expression of P-450 4A and the production of 20-HETE in the kidney of male SHR. The androgen-induced production of 20-HETE may be associated with hypertension in male SHR.
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ISSN:0385-2385
1884-0728
DOI:10.14842/jpnjnephrol1959.46.685