Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen-Deficient Rat

Estrogens and raloxifene (RAL) have beneficial effects on certain cardiovascular indices in postmenopausal women characterized by estrogen deficiency. Heme oxygenase (HO) activity is increased by 17β-estradiol (E(2)) and RAL in estrogen-deficient rat resulting in vasorelaxation mediated by carbon monoxide. We determined the expressions of HO in cardiac and aortic tissues after ovariectomy (OVX) and subsequent RAL or E(2) treatment. We investigated the effects of pharmacological inhibition of HO enzyme on the arginine vasopressin- (AVP-) induced blood pressure in vivo, the epinephrine- and phentolamine-induced electrocardiogram ST segment changes in vivo, and the myeloperoxidase (MPO) enzyme activity. When compared with intact females, OVX decreased the HO-1 and HO-2 expression, aggravated the electrocardiogram signs of heart ischemia and the blood pressure response to AVP, and increased the cardiac MPO. E(2) and RAL are largely protected against these negative impacts induced by OVX. The pharmacological inhibition of HO in E(2)- or RAL-treated OVX animals, however, restored the cardiovascular status close to that observed in nontreated OVX animals. The decreased expression of HO enzymes and the changes in blood pressure ischemia susceptibility and inflammatory state in OVX rat can be reverted by the administration of E(2) or RAL partly through its antioxidant and anti-inflammatory roles.