Xiancun Cao1, Chunle Zhou2, Jingmin Chong3, Lu Fu3, Lin Zhang2, Di Sun2, Hongjian Hou3, Yan Zhang3, Dongye Li4, Hong Sun5. 1. 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. 2. Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China; Institute of Cardiovascular Disease Research, Xuzhou Medical College, 221002 Xuzhou, China. 3. Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China. 4. Institute of Cardiovascular Disease Research, Xuzhou Medical College, 221002 Xuzhou, China. Electronic address: dongyeli@medmail.com.cn. 5. Department of Physiology, Xuzhou Medical College, 221004 Xuzhou, China. Electronic address: sunh@xzmc.edu.cn.
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. METHODS AND 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.
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. METHODS AND 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.
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