Sexual dimorphism of blood pressure in spontaneously hypertensive rats: effects of anti-androgen treatment.
The mechanisms resulting in the greater predisposition of male subjects towards hypertension were investigated in different strains of rats with genetic hypertension [spontaneously hypertensive rats of the stroke-prone strain (SHRSP) and spontaneously hypertensive rats (SHR)] and their respective normotensive controls. Blood pressure was reduced in young (9 weeks of age) hypertensive rats by (1) surgical castration, (2) treatment with the testosterone receptor antagonist cyproterone acetate (CPA), which does not elevate testosterone, or (3) with the testosterone receptor antagonist flutamide, which leads to a feedback elevation of gonadotrophic hormones and plasma testosterone. These treatments had no effect on high blood pressure in old hypertensive rats aged 25 weeks. Both androgen receptor antagonists attenuated high blood pressure development when given for the first 10 days after birth. These data clearly relate the sexual dimorphism of hypertension to testosterone produced during male brain maturation in the early phase of hypertension development. Testosterone appears not to contribute directly to the maintenance of high blood pressure in established hypertension.
Ganten
U
U
Department of Pharmacology, University of Heidelberg, Federal Republic of Germany.
Schröder
G
G
Witt
M
M
Zimmermann
F
F
Ganten
D
D
Stock
G
G
D000726:Androgen Antagonists / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D003534:Cyproterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017373:Cyproterone Acetate; D005260:Female; D005485:Flutamide / Q000494:pharmacology*; D008297:Male; D009919:Orchiectomy; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D013045:Species Specificity; D013739:Testosterone / Q000502:physiology
D000726:Androgen Antagonists; D000813:Anilides; D013739:Testosterone; D017373:Cyproterone Acetate; D005485:Flutamide; D003534:Cyproterone