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This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/R759    most recent 00595.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Dean, S. A. Articles by Leenen, F. H. H. Search for Related Content PubMed PubMed Citation Articles by Dean, S. A. Articles by Leenen, F. H. H.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

17-Estradiol downregulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats

Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada

Submitted 31 August 2004 ; accepted in final form 15 November 2004

Estrogens have been implicated in both worsening and protecting from cardiovascular disease. The effects of 17-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 (AT₁R), 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 µg/day (regular) E2 subcutaneously, and 4) OVX treated with 250 µg/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 AT₁R 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 AT₁R 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.

renin-angiotensin system; ovariectomy; autoradiography

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