17beta-estradiol downregulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats.
Estrogens have been implicated in both worsening and protecting from cardiovascular disease. The effects of 17beta-estradiol (E2) on the cardiovascular system may be mediated, at least in part, by its modulation of local tissue renin-angiotensin systems (RAS). We assessed two critical components, angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT(1)R), in the heart, lung, abdominal aorta, adrenal, kidney, and brain in four groups of female Wistar rats (n = 5-6/group): 1) sham ovariectomized, 2) ovariectomized (OVX) treated with subcutaneous vehicle, 3) OVX treated with 25 mug/day (regular) E2 subcutaneously, and 4) OVX treated with 250 mug/day (high) subcutaneous E2 for 2 or 5 wk. After 2 wk, plasma ACE activity was not altered by OVX, but it was 34-38% lower in OVX + regular E2 and OVX + high E2 rats compared with sham OVX rats, and these decreases were no longer present after 5 wk. After 5 wk, OVX alone increased ACE activity and binding densities, and AT(1)R binding densities by 15-100% in right ventricle, left ventricle (LV), kidney, lung, abdominal aorta, adrenal and several cardiovascular regulatory nuclei in the brain. These effects were, for the most part, prevented by regular E2 replacement and were reversed to decreases by high E2 treatment. This regulation of tissue ACE and AT(1)R is significant as the activity of these tissue RAS contributes to the pathogenesis and/or progression of hypertension, atherosclerosis, and LV remodeling after myocardial infarction.
Dean
Stephanie A
SA
Hypertension Unit, University of Ottawa Heart Institute, H360, 40 Ruskin Street, Ottawa, Ontario, Canada.
Tan
Junhui
J
O'Brien
Edward R
ER
Leenen
Frans H H
FH
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000033:anatomy & histology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D014018:Tissue Distribution; D014599:Uterus / Q000033:anatomy & histology
D044140:Receptor, Angiotensin, Type 1; D004958:Estradiol; D007703:Peptidyl-Dipeptidase A