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Dose‐response effect of estrogen on the kidney and heart
Author(s) -
Meng Xiaomei,
D'Ambrosio Martin Antonio,
Liao TangDong,
Yang XiaoPing
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.943.1
Subject(s) - estrogen , medicine , endocrinology , ovariectomized rat , renal function , uterus , cardiac function curve , blood pressure , kidney , adverse effect , heart failure
Recent clinical trials indicate that estrogen replacement therapy (ERT) may increase the risk of cardiovascular diseases. Here we studied whether the adverse effects of ERT are related to the doses used. Ovariectomized (OVX) mice received 17β‐estrodial (E2) at 0.001 (VL, very low), 0.42 (L, low), 4.2 (M, moderate) or 28.3 μg/d (H, high) for 60 days. E2 at moderate and high doses increased plasma estrogen levels by about 4.5‐fold. This was associated with ascites, nephrydrosis, proteinuria and fluid retention in uterus horns. Low dose of E2 restored plasma estrogen and uterus weight to levels similar to normal controls and no fluid retention or renal damage were found in this group of mice. Moderate and high doses of E2 also increased cardiac ANP mRNA expression and PKC and PI3K phospholyration. Aside from diastolic function, blood pressure and cardiac function were not altered by ERT at any given dose. These results suggest that ERT dosage could be an important determinant for a beneficial or detrimental outcome.