Reference : Oestrogen action on the myocardium in vivo: specific and permissive for angiotensin-c...
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
Oestrogen action on the myocardium in vivo: specific and permissive for angiotensin-converting enzyme inhibition.
Pelzer, Theo [> >]
de Jager, Tertia [> >]
Muck, Jenny [> >]
Stimpel, Michael [> >]
Neyses, Ludwig mailto [University of Luxembourg > Research Office]
Journal of hypertension
Yes (verified by ORBilu)
[en] Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Animals ; Blood Pressure/drug effects ; Drug Combinations ; Estradiol/analogs & derivatives/pharmacology ; Estrogen Antagonists/pharmacology ; Female ; Heart/anatomy & histology/drug effects ; Isoquinolines/pharmacology ; Myosin Heavy Chains/genetics/metabolism ; Organ Size/drug effects ; Ovariectomy ; Protein Isoforms/genetics/metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Inbred SHR ; Tetrahydroisoquinolines ; Up-Regulation
[en] OBJECTIVES: In contrast to the vasculature, it remains unclear whether oestrogens also directly affect the myocardium. In this study, we addressed basic questions regarding oestrogen effects on the myocardium, including specificity, pathophysiological relevance and potential clinical implications, with a special focus on interactions between oestrogen and angiotensin-converting enzyme (ACE) inhibitors in an established in-vivo model of cardiac hypertrophy. METHODS AND RESULTS: Female spontaneously hypertensive rats (SHR) were ovarectomized (OVX) or sham-operated and treated with 17beta-oestradiol (2 microg/kg per day subcutaneously), the oestrogen receptor antagonist ZM-182780 (250 microg/kg per day subcutaneously) and the ACE-inhibitor moexipril (10 mg/kg per day orally) alone or in combination for 3 months. Hormone replacement restored physiological oestradiol serum levels and prevented uterus atrophy. Whereas moexipril alone was ineffective in OVX rats, substitution of oestradiol restored the beneficial effect of moexipril on systolic blood pressure (-30 +/- 5 mmHg) and relative heart weight (-11 +/- 3%) in OVX rats. Oestradiol upregulated alpha-myosin heavy chain (MHC) mRNA (+37 +/- 7%) and protein expression (+43 +/- 6%) in spite of increased blood pressure in OVX rats. Simultaneous treatment with oestradiol plus moexipril most effectively shifted the ratio of alpha-/beta-MHC mRNA and protein expression towards alpha-MHC in OVX animals. Oestradiol (10 nmol/l) also upregulated alpha-MHC mRNA and protein in cultured cardiac myocytes. The oestrogen receptor antagonist ZM-182780 significantly inhibited the observed oestrogen effects. CONCLUSIONS: Oestrogen replacement is permissive for the beneficial effects of ACE-inhibition in female SHR rats. Oestrogen effects on the myocardium in vivo are specific (i.e. oestrogen receptor mediated) because they are inhibited by a pure oestrogen receptor antagonist and occur at physiological hormone levels.

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