Exercise training causes sympathoinhibition through antioxidant effect in the rostral ventrolateral medulla of hypertensive rats

Clin Exp Hypertens. 2012;34(4):278-83.
Kishi T, Hirooka Y, Katsuki M, Ogawa K, Shinohara K, Isegawa K, Sunagawa K.

The authors were interested to know whether exercise training affects sympathetic nerve activity through central mechanisms in stroke-prone spontaneously hypertensive rats (SPSHR). They performed a series of experiments to determine the role of oxidative stress and angiotensin II in this pathway. First, they implanted radio-telemetry system to measure mean arterial pressure and heart rate in both SHRSP and Wistar-Kyoto (WKY) rats. The animals were seperated into 4 groups exercise trained (Treadmill) and non exercise trained for 28 days. After 28 days, urinary norepinephrine was measured as an indicator of sympathetic nerve activity. They measured conscious baroreflex sensitivity by spontaneous sequence method. Thiobarbituric acid-reactive substances were measured from RVLM punches as an indicator of oxidative stress. Tempol, a superoxide dismutase mimetic and angiotensin II were microinjected into the RVLM to determine the pathway. The overall findings are that exercise training in SHRSP caused sympathoinhibition and improved baroreflex sensitivity and reduced oxidative stress through blocked AT1R in the RVLM.

-Madhan

Oxidative stress in the rostral ventrolateral medulla modulates excitatory and inhibitory inputs in spontaneously hypertensive rats

J Hypertens. 2012 Jan;30(1):97-106.  

Nishihara M, Hirooka Y, Matsukawa R, Kishi T, Sunagawa K.

This study aims at answering 3 important questions.

1. Determine whether chronic oxidative stress in the RVLM alters synaptic transmission through glutamatergic inputs.

2. Determine whether chronic oxidative stress in the RVLM alters synaptic transmission through GABA-ergic inputs.

3.  Determine whether chronic oxidative stress in the RVLM alters synaptic transmission through excitatory inputs from the PVN.

Adenoviral vectors encoding MnSOD was transferred into the RVLM of male SHRs and WKYs. Microinjection studies using Kynurenic acid (Glutamate receptor antagonist) and Bicuculline (GABA receptor antagonist) showed that reactive oxygen species (ROS) in the RVLM enhanced the excitatory glutamatergic inputs and reduced the GABAergic inputs to the RVLM neurons in SHRs. In addition, activation of the PVN neurons enhanced the pressor and sympathoexcitation through ROS in the RVLM. These findings suggest that ROS in the RVLM increases glutamatergic excitatory inputs and decreases GABAergic inputs in SHRs.

Madhan

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. :-)