1009 Apocynin and Losartan Improves Large Arterial Stiffness in Deoxycorticosterone Acetate-Salt-Induced Hypertensive Rats Associated with Inhibition of Local Oxidative Stress

Abstract

Objectives: Whether reactive oxygen species (ROS) involves in the arterial stiffness has not been reported. Here we observe the relationship between ROS and the structural and functional changes of large arteries, and the influence of apocynin and losartan in arterial stiffness in this model. Methods: DOCA salt hypertensive rats were generated as previous described. For apocynin treatment groups, three concentrations of apocynin or losartan were administered orally in a tap water solution. At the end of the sixth week, tail blood pressure, central blood pressure, pulse wave velocity (PWV) were measured. The structure and composition and the ROS level in throat aorta also been analyzed at the end of the study. Results: DOCA salt hypertensive rats are characterized by the increased collagen content and stiffness in aorta accompanied by the enhanced level of ROS. The higher dosages of apocynin reduced blood pressure(159.83 ± 7.99, 156.83 ± 11.47 vs 183.89 ± 9.87mmHg, P < 0.05), and PWV(5.17 ± 0.33, 5.31 ± 0.28, vs 6.21 ± 0.24m/s, P < 0.05). But only 1.5 mM Apocynin treatment reduced the collagen content in arterial wall(0.84 ± 0.04 vs 1.03 ± 0.09 mg/cm, P < 0.05)and ROS level markedly (436.50 ± 61.92 vs 781.65 ± 108.68 RLU/min/mg, P < 0.05). Losartan treatment also significantly decreased PWV (5.75 ± 0.20 vs. 6.33 ± 0.20 m/s, P < 0.05) but without altering tail blood pressure, central blood pressure and collagen content in arterial wall in DSH rats. The heightened ROS production in the aortic ring also dropped after losartan treatment. Conclusion: These results suggest that blockade of NADPH oxidase or local AT1R signaling exerts a therapeutic effect on increased arterial stiffness by reducing oxidative stress in DSH rats.