Effects of estrogens on cardiovascular structure in uninephrectomized SHRsp rats.
BACKGROUND
The risk of cardiovascular disease in uremic patients is greater in male than in female patients. Estrogens seem to play a cardioprotective role until menopause. Experimental data on the effect of estrogens on cardiovascular damage are controversial and potential underlying mechanisms especially in renal failure have not been fully clarified.


METHODS
Three-month-old female uninephrectomized stroke-prone spontaneously hypertensive (SHRsp) rats were sham-operated or ovariectomized. Subsequently, they received either vehicle (sesame oil) or 17-beta-3 benzoate estradiol (E2) (25 microg/day) or estriol (E3) (0.02 mg/day), respectively. After 3 months the animals were sacrified and the organs were harvested using pressure-controlled perfusion fixation. Stereologic parameters such as capillary length density (L(V)), mean intercapillary distance (MID), and volume density of the interstitial tissue (Vv) were quantitated. Additionally, expression of transforming growth factor-beta (TGF-beta), vascular endothelial growth factor (VEGF), flt-1, endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), endothelin A receptor (ETA) receptor, and alpha estrogen receptor was assessed using immunohistochemistry. Intramyocardial capillaries and the aorta were investigated by morphometric methods.


RESULTS
L(V) (mm/mm(3)) was significantly lower (2421 +/- 500) and MID (microm) significantly higher (22.2 +/- 2.33) in vehicle-treated uninephrectomized/ovariectomized compared to uninephrectomized/sham-ovariectomized controls (L(V) 3629 +/- 960, MID 12.7 +/- 2.7) as well as estradiol (L(V) 3340 +/- 739, MID 12.1 +/- 4.96) and estriol (L(V) 4655 +/- 618, MID 14.2 +/- 2.89) treated uninephrectomized/ovariectomized animals. The volume density of the cardiac interstitium was higher in vehicle-treated uninephrectomized/ovariectomized animals compared to uninephrectomized/sham-ovariectomized, estradiol and estriol treated uninephrectomized/ovariectomized rats. The protein level expression of TGF-beta was higher in vehicle treated uninephrectomized/ovariectomized compared to uninephrectomized/sham and all treatment groups.


CONCLUSIONS
In ovariectomized SHRsp rats with moderate renal failure cardiac lesions were strikingly less after estradiol or estriol treatment. The results document a beneficial role of estrogens on cardiac abnormalities in a model of moderate renal dysfunction.
Gross
Marie-Luise
ML
Department of Pathology, University of Heidelberg, Heidelberg, Germany. Marie-Luise_Gross@med.uni-heidelberg.de
Ritz
Eberhard
E
Korsch
Michael
M
Adamczak
Marcin
M
Weckbach
Monika
M
Mall
Gerhard
G
Berger
Irina
I
Hansen
Alexander
A
Amann
Kerstin
K
D000818:Animals; D001011:Aorta / Q000473:pathology; D001160:Arterioles / Q000473:pathology; D019332:Endothelin-1 / Q000032:analysis / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D007150:Immunohistochemistry; D009206:Myocardium / Q000473:pathology*; D009392:Nephrectomy; D019001:Nitric Oxide Synthase / Q000032:analysis; D052250:Nitric Oxide Synthase Type III; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D051437:Renal Insufficiency / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D019332:Endothelin-1; D004967:Estrogens; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat