Abstract
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 (E2) 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 E2 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. E2 and RAL are largely protected against these negative impacts induced by OVX. The pharmacological inhibition of HO in E2- 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 E2 or RAL partly through its antioxidant and anti-inflammatory roles.
Highlights
The clinical cardiovascular outcome study results in postmenopausal women are inconsistent and disappointing so far [1], estrogens demonstrated cardiovascular protective effects in various conditions and play an important role in the sex-related differences of hypertension in experimental models
Ovariectomy was found to lead to significantly decreased cardiac Heme oxygenase (HO) expression (HO-1: 39.86 ± 4.79%; HO-2: 48.0 ± 2.76%), and E2 (HO-1: 95.14 ± 4.11%; HO-2: 100.14 ± 4.02%) or RAL (RAL 0.33, HO-1: 79.5 ± 3.42%; HO-2: 87.55 ± 3.85%, RAL 1, HO-1: 90.29 ± 4.43%; HO-2: 95.86 ± 4.03%) supplementation in the OVX rats completely restored the HO expression to the level observed in the heart of the ovaryintact females
We have demonstrated cardiovascular protective features of E2 and RAL mediated by the HO system in OVX female rats
Summary
The clinical cardiovascular outcome study results in postmenopausal women are inconsistent and disappointing so far [1], estrogens demonstrated cardiovascular protective effects in various conditions and play an important role in the sex-related differences of hypertension in experimental models. Estrogen receptor-dependent and independent pathways result in favourable changes in plasma lipoproteins, haemostatic factors, glucose metabolism, and endotheliumderived factors as well as in the inhibition of smooth muscle cell migration and proliferation. Estrogen reduces both the myocardial infarct size and the occurrence of ischemiareperfusion-induced damage and neutrophil infiltration in cardiac muscle [2]. In addition to their specific, receptormediated effects, estrogens have antioxidant properties related to their aromatic/phenolic chemical structure: ovariectomy results in increased myeloperoxidase (MPO) enzyme activity [3, 4]. Estrogen replacement therapy has antioxidant properties and attenuates neutrophil infiltration and myeloperoxidase (MPO) activity in the heart [2]
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