Estrogen modulates the emotional stress- and catecholamine-induced acute heart failure

Abstract

Emotional stress triggers takotsubo cardiomyopathy in postmenopausal women. Clinical analysis of autonomic nervous function has revealed a transient increase of sympathetic nervous activity and decrease of vagal nervous activity. Immobilization stress (IMO) of rats can reproduce the ECG and LVG changes that occur in takotsubo cardiomyopathy, both of which are prevented by combined blockade of α- and β-adrenoceptors. Estrogen supplementation partially attenuated these cardiac changes. It also attenuated the IMO-induced increase of c-Fos immunoreactivity, c-fos mRNA expression in the lateral septum, medial amygdaloid nucleus, paraventricular hypothalamic nucleus, dorsomedial hypothalamic nucleus, laterodorsal tegmental nucleus and locus coeruleus; these regions contain central sympathetic neurons and neurons with immunoreactive estrogen receptors. It also down-regulated c-fos mRNA expression in the adrenal gland and the heart, suggesting an increase of estrogen attenuated the stress-induced hypothalamo-sympatho-adrenal outflow from the central nervous system to the target organs. In addition, estrogen treatment up-regulated the levels of some cardio-protective substances such as ANP and HSP70 in the heart. These data suggest that reduction of estrogen levels following menopause might be involved in the primary cause of takotsubo cardiomyopathy both by indirect action on the nervous system and by direct action on the heart.