title: The influence of oestrogen-deficiency and ACE inhibition on the progression of myocardial hypertrophy in spontaneously hypertensive rats.
abstract: BACKGROUND
  ACE inhibitors are widely used to antagonize the biological activity of angiotensin II in hypertensive heart disease. Oestrogen reduces angiotensin type 1 receptor expression, and thereby modifies angiotensin signalling.
  
  
  OBJECTIVE
  To investigate the interaction of oestrogen status and ACE inhibition on the development of left ventricular hypertrophy and expression of transforming growth factor (TGF)-beta(1) in female spontaneously hypertensive rats (SHR).
  
  
  RESULTS
  Intact female SHR, ovariectomised SHR, and ovariectomised SHR with 17beta-oestradiol (E2) replacement therapy were either treated with placebo or the ACE inhibitor moexiprilat. Blood pressure, left ventricular hypertrophy, and expression of TGF-beta(1) and TGF-beta(1)-regulated genes were investigated. ACE inhibition reduced blood pressure in all groups. When normalised to blood pressure, a significant reduction in hypertrophy was found in ovariectomised animals receiving E2. Expression of TGF-beta(1) was increased in all three groups treated with the ACE inhibitor, with top levels in ovariectomised animals. Moreover, expression of ornithine decarboxylase (ODC), an adrenoceptor dependent gene, downstream of TGF-beta(1), was up-regulated upon ACE inhibition, except in animals which were ovariectomised and oestrogen supplemented. Parathyroid hormone-related peptide, a growth factor negatively regulated by TGF-beta(1), was down-regulated in all animals receiving the ACE inhibitor.
  
  
  CONCLUSIONS
  ACE inhibition modulated TGF-beta(1) and TGF-beta(1) dependent genes. Oestrogen deficiency alone did not influence the progression of cardiac hypertrophy in this model of female SHR.
authors.affiliation: Medizinische Universitäts-Poliklinik, Universitätsklinikum Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: van Eickels
authors.forename: Rolf
authors.initials: R
authors.lastname: Schreckenberg
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Rainer
authors.initials: R
authors.lastname: Meyer
authors.forename: Christian
authors.initials: C
authors.lastname: Grohé
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Schlüter
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D018450:Disease Progression; D004958:Estradiol / Q000627:therapeutic use; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D011918:Rats, Inbred SHR; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004967:Estrogens; D044005:Tetrahydroisoquinolines; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004958:Estradiol; C059506:moexiprilat