Estrogen Replacement Reduces Oxidative Stress in the Rostral Ventrolateral Medulla of Ovariectomized Rats

Fan Hao et. al.

Oxidative Medicine and Cellular Longevity

              It is well known that the incidence of cardiovascular disease increases in women after they go through menopause. The reasons behind this effect are unclear, but it is thought that the hormones that are circulating in the blood prior to menopause have some sort of protective effect against cardiovascular disease. Specifically, estrogen has been shown to modulate activity in the central nervous system. It is well known that the Rostral Ventrolateral Medulla (RVLM) is a key regulator of sympathetic outflow for the cardiovascular system. It has been shown that over activity of the RVLM is implicated in cardiovascular disease and that there is higher sympathetic outflow in ovariectomized rats. This suggests that the ovarian hormones may be playing a role in decreasing sympathetic outflow and thus the incidence of cardiovascular disease in pre-menopausal women. Increased oxidative stress due to reactive oxygen species have been implicated in development of hypertension. Oxidative stress is primarily due to an imbalance of the formation and removal of reactive oxygen species. NADPH oxidase will form a superoxide and superoxide dismutase will catalyze the breakdown of the superoxide to oxygen or hydrogen peroxide. Thus, a measurement of the relative activity of NADPH oxidase and superoxide dismutase provides a measurement of oxidative stress. Oxidative stress in the RVLM has been associated with increased sympathetic outflow and hypertension. The aim of the present study was to assess the level of oxidative stress in the RVLM of ovariectomized rats with and without estrogen replacement.

              Sprague-Dawley rats were assigned to one of four groups: ovariectomy with estrogen, ovariectomy with vehicle, sham with estrogen and sham with vehicle. Sham groups had the same operation as the ovariectomy group but did not have the ovaries removed. One week after the procedure the estrogen groups were treated with 17-beta-estradiol for four weeks via subcutaneous injections. The vehicle groups had the same injections but with 0.9% normal saline. Periodically rats had cardiovascular measurements of mean arterial pressure and heart rate as well as measurements of renal sympathetic nerve activity. Rats were then sacrificed, and levels of superoxide dismutase and NAPDH oxidase were measured in brain slices via western blotting.

              Results of the study are as follows. 6 weeks after ovariectomy rats showed significant increases in blood pressure, heart rate and renal sympathetic nerve activity, this affect was completely prevented by the injection of estrogen for 4 weeks. Levels of reactive oxygen species in the RVLM were assessed by fluorescent labeling showed that there was significantly more reactive oxygen species in the RVLM in the ovariectomy group that in the sham group and that this was reduced by estrogen replacement. Ovariectomized rats showed a higher level of NADPH oxidase and a lower level of superoxide dismutase as compared to the sham group. This effect was attenuated by estrogen replacement. This was as expected due to the fact that a higher ratio of NADPH oxidase: superoxide dismutase would align with a higher level of reactive oxygen species. These data suggest that the estrogen replacement in ovariectomized rats decreases the blood pressure and sympathoexcitation and that the mechanism behind this may be from an estrogen dependent reduction in oxidative stress in the RVLM via changes in protein expression.

              I thought that this paper was a good paper to blog this week because of where I would like to go in the lab with the running data. I would like to see what the effect of ovariectomy and estrogen replacement is on the voluntary wheel running of rats and I would like to investigate the role that estrogen has in modulating the activity of the RVLM.

- Ben