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Horm Metab Res 2010; 42(2): 130-136
DOI: 10.1055/s-0029-1241807
Animals, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Rhythmic Supplementation of 17β-Estradiol According to the Physiological Estrous Cycle: Effect on Blood Pressure in Female Ovariectomized Rats

A. Grundt1 [*] , C. Grundt1 [*] , K. Knoth1 , B. Lemmer1
  • 1Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, Ruprecht-Karls-Universität Heidelberg, Mannheim, Germany
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Publikationsverlauf

received 13.08.2009

accepted 05.10.2009

Publikationsdatum:
30. Oktober 2009 (online)

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Abstract

Female Wistar-Kyoto rats (WKY) show a 4-day estrous cycle. The aim of this study was to examine the impact of 17β-estradiol supplementation every fourth day to ovariectomized rats – mimicking the physiological estrous cycle – on regulation of blood pressure. We monitored blood pressure telemetrically in intact females, ovariectomized (OVX), and ovariectomized WKY injected subcutaneously with 17β-estradiol (OVXE2) in a 4-day rhythm for 24 weeks. Blood pressure decreased both in intact females and OVXE2, whereas that of OVX persisted at constant levels. The underlying mechanisms studied include the nitric oxide pathway, the rennin-angiotensin system as well as the endothelin system. Serum and urinary nitrate/nitrite (NOx) as well as aortic eNOS decreased in OVX and were restored to normal in OVXE2. Conversely, caveolin-1 was higher in OVX than in intact females and OVXE2 while Hsp90 did not differ among groups. Plasma angiotensin II and aortic AT1 receptor expression increased in OVX and were normalized in OVXE2. AT2 receptor expression was regulated reciprocally. Serum endothelin-1 was significantly elevated in OVX and OVXE2. There was no difference in aortic ETA receptor expression between groups whereas ETB receptor expression was higher in intact females and OVXE2 than in OVX. The study suggests that supplementation of 17β-estradiol in female WKY according to the natural estrous cycle maintains the physiological blood pressure encompassing vasorelaxing and vasoconstricting pathways. The physiological estrous cycle should be kept in mind when cardiovascular data are to be collected/interpreted under estrogen supplementation.

Key words

hypertension - estradiol deficiency/supplementation - nitric oxide - rennin-angiotensin-aldosterone system - endothelin system

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1 Both authors contributed equally to the work.

Correspondence

Prof. Dr. med. Dr. h.c.B. Lemmer

Institute of Experimental and Clinical Pharmacology and Toxicology

Medical Faculty Mannheim

Ruprecht-Karls-Universität Heidelberg

Maybachstrasse 14

68169 Mannheim

Germany

Telefon: +49/621/383 97 04

Fax: +49/621/383 97 11

eMail: bjoern.lemmer@pharmtox.uni-heidelberg.de