Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats

Aim: Endothelial dysfunction is considered a premature indication of atherosclerosis and vessel damage and is present in the postmenopausal period. This study compares the influence of estrogen, raloxifene and tamoxifen on factors that affect endothelial function in ovariectomized (OVX) rats. Main methods: The rats were divided into: SHAM; OVX; OVX + estrogen (0.5 mu g/kg/day); OVX + raloxifene (2 mg/kg/day) and OVX + tamoxifen (1 mg/kg/day) groups. The acetylcholine vasorelaxation response was evaluated in the mesenteric vascular bed. The vascular oxidative stress and serum inflammatory cytokine levels were monitored, and analyses of eNOS and iNOS were performed. Key findings: The acetylcholine-induced responses obtained in the OVX were lower than those obtained in the SHAM, and all treatments restored this response. L-NAME reduced and equalized the acetylcholine-induced response in all groups. The attenuation of the acetylcholine-induced responses by aminoguanidine was greater in the OVX. Endothelial dysfunction in OVX was associated with oxidative stress and an increase in iNOS and decrease in eNOS expression. Except for the production of reactive oxidative species (ROS) in the OVX + tamoxifen, treatments improved the nitric oxide component of the relaxation response and normalized both the oxidative stress and the expression of those signaling pathway enzymes. Serum levels of TNF-alpha and IL-6 were increased in OVX, and treatments normalized these levels. Significance: Raloxifene and tamoxifen have similar anti-inflammatory effects that may be important in improving vascular dysfunction. Tamoxifen did not affect the ROS but improved endothelial dysfunction. The protective effect on endothelial function by these treatments provides evidence of their potential cardiovascular benefits in the postmenopausal period. (C) 2015 Elsevier Inc. All rights reserved.