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

Takashi Ueyama; Fuminobu Ishikura; Akiko Matsuda; Toshihiko Asanuma; Kazuki Ueda; Masao Ichinose; Ken Kasamatsu; Takuzo Hano; Takashi Akasaka; Yoshihiro Tsuruo; Keiko Morimoto; Shintaro Beppu

doi:10.1253/circj.71.565

Experimental Investigation

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

Takashi Ueyama, Fuminobu Ishikura, Akiko Matsuda, Toshihiko Asanuma, Kazuki Ueda, Masao Ichinose, Ken Kasamatsu, Takuzo Hano, Takashi Akasaka, Yoshihiro Tsuruo, Keiko Morimoto, Shintaro Beppu

Author information

Takashi Ueyama
Department of Anatomy and Cell Biology, Wakayama Medical University
Fuminobu Ishikura
Division of Functional Diagnostic Science, Osaka University Graduate School of Medicine
Akiko Matsuda
Division of Functional Diagnostic Science, Osaka University Graduate School of Medicine
Toshihiko Asanuma
Division of Functional Diagnostic Science, Osaka University Graduate School of Medicine
Kazuki Ueda
Second Department of Internal Medicine, Wakayama Medical University
Masao Ichinose
Second Department of Internal Medicine, Wakayama Medical University
Ken Kasamatsu
Department of Cardiovascular Medicine, Wakayama Medical University
Takuzo Hano
Department of Cardiovascular Medicine, Wakayama Medical University
Takashi Akasaka
Department of Cardiovascular Medicine, Wakayama Medical University
Yoshihiro Tsuruo
Department of Anatomy and Cell Biology, Wakayama Medical University
Keiko Morimoto
Department of Enviromental Health, Faculty of Life Science and Human Technology, Nara Women's University
Shintaro Beppu
Division of Functional Diagnostic Science, Osaka University Graduate School of Medicine

Keywords: Emotional stress, Estrogen, Paraventricular hypothalamic nucleus, Sympathetic nervous system

JOURNAL FREE ACCESS

2007 Volume 71 Issue 4 Pages 565-573

DOI https://doi.org/10.1253/circj.71.565

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Abstract

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. (Circ J 2007; 71: 565 - 573)

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