Chronic estradiol-17β exposure increases superoxide production in the rostral ventrolateral medulla and causes hypertension: reversal by resveratrol

This very well-written study investigates the effect of chronic exposure to estradiol on blood pressure regulation in female rats. It is known that hormone replacement therapy (HRT) in post-menopausal women causes a slight, but significant, increase in blood pressure and cardiovascular disease risk. In addition, a large number of young women in industrialized countries take forms of estrogen orally for contraceptive purposes. Since the rostral ventrolateral medulla plays such an important role in blood presure control, they focused on changes occurring in the RVLM associated with changed in blood pressure. Specifically, they were interested in superoxide production since many studies have shown increased oxidative stress in the RVLM of animal models of cardiovascular disease.
Female rats were implanted with slow release estradiol pellets, or not, for three months. During the third month they were implanted with radiotelemetry transmitters and their BP was monitored for about two weeks. At the end of the experimental period, animals were sacrificed. Brains and trunk blood were removed and frozen for later study. In a second experiement, estradiol implanted and sham animals were divided into two groups, one recieving the antioxidant resveratrol in their food and the other not. Animals were sacrificed at the end of the 2nd experiment as in the 1st.
The author's original hypothesis was right. They showed that animals recieving chronic estradiol developed higher blood pressures than those who did not. Also, treated animals were shown to have increased superoxide levels in the RVLM. Most interesting was that treatment with resveratrol reversed these deleterious effects. These data suggest that increases in blood pressure seen in women recieving HRT and young women on contraceptive therapy may be due to oxidative stress in the RVLM. This effect can be mitigated by simply adding resveratrol in the diet. "A glass of red wine for me keeps my RVLM happy"
Althought these data are interesting and certainly compelling, the study could have been greatly strengthened by adding an additional group of ovarectomized animals. This would make the study much more applicable to post-menopausal women recieving HRT. For shame authors, for shame. :-)