Chronic estrogen supplementation following ovariectomy improves the emotional stress-induced cardiovascular responses by indirect action on the nervous system and by direct action on the heart.
BACKGROUND
Takotsubo cardiomyopathy is triggered by emotional or physical stress especially in post-menopausal women. A reduction in estrogen levels following menopause might underlie the high incidence of takotsubo cardiomyopathy.


RESULTS
The left ventricular contraction between ovariectomized rats (OVX) and OVX with estrogen supplementation (OVX + E) while subjected to immobilization stress (IMO) was compared. The IMO in combination with general anesthesia impaired the left ventricular contraction in both OVX and OVX + E. Estrogen supplementation tended to improve the IMO-induced cardiac dysfunction and significantly attenuated the increase of blood pressure and heart rate. To understand the protective mechanism of estrogen, the expression of c-fos mRNA, a marker of cellular activation was compared. The mRNA expression of cardioprotective substances in the heart was also investigated. In the OVX + E, the levels of c-fos mRNA were significantly decreased in the paraventricular hypothalamic nucleus, adrenal gland and left ventricle, suggesting that an increase of estrogen attenuates the emotional stress-induced hypothalamo-sympatho-adrenal outflow from the central nervous system to the target organs. An expression of heat shock protein 70 and atrial natriuretic peptide was significantly augmented in the OVX + E.


CONCLUSIONS
These data suggest that estrogen supplementation partially prevents emotional stress-induced cardiovascular responses both by indirect action on the nervous system and by direct action on the heart.
Ueyama
Takashi
T
Department of Anatomy and Cell Biology, Wakayama Medical University, Wakayama, Japan. tueyama@wakayama-med.ac.jp
Ishikura
Fuminobu
F
Matsuda
Akiko
A
Asanuma
Toshihiko
T
Ueda
Kazuki
K
Ichinose
Masao
M
Kasamatsu
Ken
K
Hano
Takuzo
T
Akasaka
Takashi
T
Tsuruo
Yoshihiro
Y
Morimoto
Keiko
K
Beppu
Shintaro
S
D000818:Animals; D004195:Disease Models, Animal; D004343:Drug Implants; D004452:Echocardiography; D004967:Estrogens / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009420:Nervous System / Q000187:drug effects*; D010052:Ovariectomy; D017698:Postmenopause; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000150:complications*; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000517:prevention & control*
D004343:Drug Implants; D004967:Estrogens; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger