title: Estrogen resisted stress-induced cardiomyopathy through increasing the activity of β₂AR-Gαs signal pathway in female rats.
abstract: BACKGROUND
  Stress-induced cardiomyopathy (SCM) is characterized by transient left ventricular systolic dysfunction. Over 90% of SCM patients are postmenopausal women, suggesting that the incidence of SCM is associated with low level of estrogen. Previous studies have shown that high levels of epinephrine (EPI) triggered SCM by switching β2-adrenoceptor (β2AR) coupling from Gαs to Gαi signaling pathway. This study examined whether estrogen protected myocardium against SCM through modulating the β2AR-G proteins signal pathway.
  
  
  RESULTS
  Female Sprague-Dawley (SD) rats were divided into sham operation (Sham) and ovariectomized (OVX) groups. Six weeks after ovariectomy, the plasma levels of EPI and norepinephrine significantly increased. Then they were injected with EPI to make SCM models. Lack of estrogen resulted in more serious cardiac dysfunction and higher cardiac troponin I (cTnI) concentration in acute EPI surge. Pretreatment with ICI118,551 abolished the discrepancy induced by ovariectomy. Pretreatment with clenbuterol aggravated the difference of left ventricular hemodynamics between Sham and OVX rats. Blocking Gαi abolished the cardiomyocyte contractile inhibition by high levels of EPI. Estrogen deficiency decreased the concentration of cAMP and the phosphorylation of PKA in OVX+EPI group. After EPI injection for 20 min, acute estrogen supplementation could increase the concentration of cAMP and the phosphorylation of PKA in OVX rats suffered EPI-induced injury.
  
  
  CONCLUSIONS
  Our results showed that estrogen improved the inhibitory effects of myocardial contraction induced by high levels of EPI. Estrogen protected myocardium against SCM via increasing the activity of β2AR-Gαs signal pathway and decreasing the concentration of catecholamine in plasma.
authors.affiliation: Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China; Institute of Cardiovascular Disease Research, Xuzhou Medical College, 221002 Xuzhou, China; Department of Cardiology, Jining NO.1 People's Hospital, 272011 Jining, China.
authors.forename: Xiancun
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China; Institute of Cardiovascular Disease Research, Xuzhou Medical College, 221002 Xuzhou, China.
authors.forename: Chunle
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Chong
authors.affiliation: Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China; Institute of Cardiovascular Disease Research, Xuzhou Medical College, 221002 Xuzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China; Institute of Cardiovascular Disease Research, Xuzhou Medical College, 221002 Xuzhou, China.
authors.forename: Di
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, 221002 Xuzhou, China. Electronic address: dongyeli@medmail.com.cn.
authors.forename: Dongye
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China. Electronic address: sunh@xzmc.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D004837:Epinephrine / Q000097:blood; D004967:Estrogens / Q000502:physiology* / Q000627:therapeutic use; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D054549:Takotsubo Cardiomyopathy / Q000097:blood / Q000209:etiology* / Q000517:prevention & control
chemical_list: D004967:Estrogens; D018343:Receptors, Adrenergic, beta-2; D004837:Epinephrine
keywords: Cardiomyopathy; Epinephrine; Estrogen; G proteins; β-Adrenoceptors