17beta-estradiol attenuates cardiac dysfunction and decreases NF-kappaB binding activity in mechanically stretched rat hearts.
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 17beta-estradiol (100nM) and the other group hearts (n=6) were perfused with estrogen plus its receptor antagonist ICI182,780 (1microM) 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-kappaB (NF-kappaB) 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-kappaB DNA binding activity were significantly increased following myocardial stretching. In 17beta-estradiol treated hearts, the myocardial functions were significantly improved. The levels of TNF-alpha, phospho-p38 MAPK, and NF-kappaB 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 17beta-estradiol on the stretched hearts were abolished by ICI182,780. The results suggest that pharmacological dose of 17beta-estradiol will attenuate stretching-induced cardiac dysfunction in an isolated heart model. The mechanisms could involve in blunting p38 MAPK and NF-kappaB signaling.
Li
Jing
J
Department of Pathophysiology, Nanjing Medical University, Nanjing 210029, China.
Wu
Meiling
M
Que
Lingli
L
Wang
Yongmei
Y
Xu
Xuan
X
Hu
Yulong
Y
Ha
Tuanzhu
T
Li
Chuanfu
C
Chen
Qi
Q
Li
Yuehua
Y
D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006331:Heart Diseases / Q000378:metabolism / Q000503:physiopathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D007770:L-Lactate Dehydrogenase; D048051:p38 Mitogen-Activated Protein Kinases