Impaired Endothelial Function in Ovariectomised Rats: Effects of Tempol

Abstract

Menopause causes endothelial dysfunction. We investigated the hypothesis that reactive oxygen species (ROS) mediate the adverse effects of ovariectomy (OVX) on microvessels. Mesenteric arterioles (MAs) were isolated from rats 4–6 weeks after sham‐operation (S) or OVX alone, S or OVX rats were given vehicle or tempol (2 mmol · l−1) throughout (n=6/group) to measure endothelium derived relaxation factor (EDRF) and endothelium dependent contracting factor (EDCF) using a wire myograph. NO and ROS were quantitated by DAF‐FM and tempo‐9AC‐fluorescence using RatioMasterTM. OVX rats had increased mean blood pressure (MBP) (114±7 vs 88±6.5 mmHg, P<0.05). Their MAs had increased medium:lumen ratio (4.44±0.38 vs 1.54±0.29, P<0.01) and EDRF (20±4 vs 41±4%, P<0.001) and decreased NO activity (0.37±0.1 vs 0.7±0.1 Units, P<0.01). However, OVX rats developed a new EDCF response (20±6 vs 5±5%, P<0.05) accompanied by increased ROS activity (0.22±0.09 vs 0.10±0.01 units; P<0.01). Tempol prevented significant changes in BP, vascular remodeling, EDRF and NO activity, and prevented any EDCF or ROS responses in OVX rats. In conclusion, OVX causes hypertension and microvascular remodeling and redirects endothelial responses from relaxation to contraction accompanied by reduced vascular NO and enhanced ROS. All of these effects are dependent on ROS and could, therefore, be targeted with effective antioxidant therapy.