title: Endothelial dysfunction and oxidative stress during estrogen deficiency in spontaneously hypertensive rats.
abstract: BACKGROUND
  Postmenopausal estrogen deficiency is associated with an increased cardiovascular risk, hypertension, and oxidative stress. Angiotensin type 1 (AT(1)) receptor regulation is involved in the pathogenesis of atherosclerosis. To characterize vascular function, oxidative stress, and AT(1) receptor regulation during estrogen deficiency, ovariectomized spontaneously hypertensive rats (SHR) were investigated in comparison with sham-operated animals and with ovariectomized rats receiving estrogen replacement therapy with 17beta-estradiol.
  
  
  RESULTS
  Arterial blood pressure was similar in all 3 groups investigated. Five weeks after ovariectomy, endothelial dysfunction in aortic rings was observed, which was reversed by estrogen replacement therapy. Estrogen deficiency led to an enhanced vasoconstriction by angiotensin II. Vascular superoxide production was significantly increased compared with that in sham-operated rats, as measured by lucigenin chemiluminescence assays. Estrogen substitution normalized the production of free radicals in the vessel wall. Vascular AT(1) receptor expression was significantly upregulated by estrogen deficiency, as shown by quantitative reverse transcription-polymerase chain reaction, whereas endothelial NO synthase mRNA expression and NO release were unchanged. Five-week treatment of the animals with the AT(1) receptor antagonist irbesartan prevented endothelial dysfunction in ovariectomized rats and normalized the vascular production of free radicals.
  
  
  CONCLUSIONS
  In SHR, estrogen deficiency leads to increased vascular free radical production and enhanced angiotensin II-induced vasoconstriction via increased vascular AT(1) receptor expression, resulting in endothelial dysfunction. Estrogen replacement therapy and AT(1) receptor antagonism prevent these pathological changes. Therefore, estrogen deficiency-induced AT(1) receptor overexpression and oxidative stress may play an important role in cardiovascular diseases associated with menopause.
authors.affiliation: Medizinische Klinik und Poliklinik, Innere Medizin III, Universitätskliniken des Saarlandes, Homburg/Saar, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Wassmann
authors.forename: A T
authors.initials: AT
authors.lastname: Bäumer
authors.forename: K
authors.initials: K
authors.lastname: Strehlow
authors.forename: M
authors.initials: M
authors.lastname: van Eickels
authors.forename: C
authors.initials: C
authors.lastname: Grohé
authors.forename: K
authors.initials: K
authors.lastname: Ahlbory
authors.forename: R
authors.initials: R
authors.lastname: Rösen
authors.forename: M
authors.initials: M
authors.lastname: Böhm
authors.forename: G
authors.initials: G
authors.lastname: Nickenig
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004958:Estradiol / Q000008:administration & dosage; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D000077405:Irbesartan; D010052:Ovariectomy; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004967:Estrogens; D005609:Free Radicals; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D013481:Superoxides; D000804:Angiotensin II; D004958:Estradiol; D000077405:Irbesartan