[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 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.
Ishizuka
Tsuneo
T
Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Japan.
Ito
Osamu
O
Omata
Ken
K
Ito
Sadayoshi
S
D000728:Androgens / Q000502:physiology*; D000818:Animals; D042926:Cytochrome P-450 CYP4A / Q000378:metabolism; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012737:Sex Factors; D013739:Testosterone / Q000097:blood
D000728:Androgens; D006893:Hydroxyeicosatetraenoic Acids; D013739:Testosterone; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D042926:Cytochrome P-450 CYP4A