Orchidectomy, but not ovariectomy, regulates angiotensin II-induced vascular diseases in apolipoprotein E-deficient mice.
In humans, the incidence and severity of abdominal aortic aneurysms (AAA) are greater in males than in females. Chronic infusion of angiotensin II (AngII) into apolipoprotein E-deficient (apoE(-/-)) mice promotes atherosclerosis and causes the formation of AAAs. Just as human males are more susceptible to developing AAAs, male mice are more susceptible to AngII-induced AAAs. We hypothesized that sex steroid hormones mediate gender differences in AngII-induced AAA through regulation of the renin-angiotensin system. To define the role of ovarian hormones, female apoE(-/-) mice were subjected to ovariectomy or sham operation and infused with AngII (1000 ng/kg x min) for 28 d. Ovariectomy had no effect on AngII-induced atherosclerosis, nor did it influence the incidence or severity of AAA. To define the role of testicular hormones, male apoE(-/-) mice were subjected to orchidectomy (orx) or sham operation and infused with AngII (1000 ng/kg x min) for 28 d. Orx resulted in a profound reduction in AAA incidence (85% vs. 18%, sham vs. orx; P = 0.003) to the level observed in females (25%). However, orx had no effect on AngII-induced reductions in plasma renin concentration or spleen AngII receptor density. In contrast, orx resulted in an increase in atherosclerosis (0.46 +/- 0.07 vs. 1.20 +/- 0.21 mm(2), sham vs. orx; P = 0.002). These results suggest that estrogen does not mediate gender differences in AngII-induced AAA. In contrast, androgens mediate a higher incidence of AngII- induced AAA, through mechanisms that do not appear to involve circulating renin or angiotensin receptor density.
Henriques
Tracy A
TA
Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536-0082, USA.
Huang
Jing
J
D'Souza
Susan S
SS
Daugherty
Alan
A
Cassis
Lisa A
LA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced*; D001057:Apolipoproteins E / Q000502:physiology*; D001161:Arteriosclerosis / Q000139:chemically induced*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009919:Orchiectomy; D010052:Ovariectomy; D012727:Sex Characteristics
D001057:Apolipoproteins E; D012739:Gonadal Steroid Hormones; D000804:Angiotensin II