Estrogen resisted stress-induced cardiomyopathy through increasing the activity of β2AR–Gαs signal pathway in female rats
2015
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 β 2 -adrenoceptor (β 2 AR) coupling from Gαs to Gαi signaling pathway. This study examined whether estrogen protected myocardium against SCM through modulating the β 2 AR-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 20min, 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 β 2 AR–Gαs signal pathway and decreasing the concentration of catecholamine in plasma.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
39
References
27
Citations
NaN
KQI