Cardioprotective effects of long-term treatment with raloxifene, a selective estrogen receptor modulator, on myocardial ischemia/reperfusion injury in ovariectomized rats.
OBJECTIVE
The aim of this study was to investigate the beneficial effect of long-term treatment with raloxifene (RAL), a selective estrogen receptor modulator, on myocardial ischemia/reperfusion (MI/R) injury in ovariectomized (Ovx) rats.


METHODS
Ovariectomy was performed in female Sprague-Dawley rats 8 weeks old. Ovx rats were treated with RAL 1 or 5 mg/kg (gavage, once daily) or 17beta-estradiol (E2; 50 microg/kg SC, three times a week) for 8 weeks. The cardioprotective effect of RAL was evaluated in an open-chest anesthetized rat model of MI/R, which was induced by 40-minute left coronary artery occlusion and 100-minute reperfusion.


RESULTS
Long-term treatment with RAL 1 mg/kg significantly suppressed the duration of ventricular tachycardia elicited by MI. After MI/R, the levels of plasma creatine kinase-MB fraction and lactate dehydrogenase in Ovx rats were significantly higher than those in the sham group, which were significantly reduced by long-term treatment with RAL 1 mg/kg or E2. Neutrophil myeloperoxidase activity in ischemic myocardium markedly increased in the Ovx group, whereas long-term treatment with RAL 1 or 5 mg/kg or E2 significantly suppressed the elevation of myeloperoxidase activity. After MI/R, the protein expression of phosphorylated inhibitory kappaBalpha and caspase-3 in ischemic myocardium pronouncedly increased in the Ovx group and was attenuated by long-term treatment with RAL 1 mg/kg or E2.


CONCLUSIONS
Long-term treatment with RAL can reduce the severity of MI-induced arrhythmias and attenuate MI/R-induced damages and apoptosis in Ovx rats. This cardioprotective effect of RAL may be associated with inhibition of neutrophil infiltration and suppression of nuclear factor-kappaB activation.
Chung
Ming-Ting
MT
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan.
Cheng
Pao-Yun
PY
Lam
Kwok-Keung
KK
Chen
Shu-Ying
SY
Ting
Yi-Fan
YF
Yen
Mao-Hsiung
MH
Lee
Yen-Mei
YM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D009203:Myocardial Infarction; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010052:Ovariectomy; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage*; D017180:Tachycardia, Ventricular / Q000517:prevention & control*; D013995:Time
D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol