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. METHODS AND 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.