This study was to examine the effect of estrogen on mechanical stretching-induced cardiac dysfunction in an isolated heart model. The isolated rat hearts were perfused via the Langendorff system and exposed to left ventricular stretching. One group hearts (n = 6) were perfused with 17β-estradiol (100 nM) and the other group hearts (n = 6) were perfused with estrogen plus its receptor antagonist ICI182,780 (1 μM) before myocardial stretching was performed. Control hearts (n = 6) were perfused with perfusion buffer. Cardiac functions were recorded. At the end of perfusion, the hearts were harvested and the levels of tumor necrosis factor-alpha (TNF-alpha), phospho-p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) binding activity were examined. Acute ventricular stretching resulted in significantly decrease in left ventricular developed pressure (LVDP) by 42.7%, maximal positive and negative values of the first derivative of pressure (+dP/dt and -dP/dt) by 43.2%, and 43.5%, respectively. The levels of TNF-alpha, phospho-p38 MAPK and NF-κB DNA binding activity were significantly increased following myocardial stretching. In 17β-estradiol treated hearts, the myocardial functions were significantly improved. The levels of TNF-alpha, phospho-p38 MAPK, and NF-κB binding activity in myocardium were also significantly reduced by 35.7%, 56.9%, and 50%, respectively, compared with untreated stretched hearts. The beneficial effects of 17β-estradiol on the stretched hearts were abolished by ICI182,780. The results suggest that pharmacological dose of 17β-estradiol will attenuate stretching-induced cardiac dysfunction in an isolated heart model. The mechanisms could involve in blunting p38 MAPK and NF-κB signaling.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-18741 |
| Date | 01 August 2008 |
| Creators | Li, Jing, Wu, Meiling, Que, Lingli, Wang, Yongmei, Xu, Xuan, Hu, Yulong, Ha, Tuanzhu, Li, Chuanfu, Chen, Qi, Li, Yuehua |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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