Jiu-Qiong Yan, Fang Huang, Fan Hao, Xiao-ling Su, Qi Meng, Ming-Juan Xu (October 2017)
Pre-eclampsia (PE) is a disorder that occurs during pregnancy and is characterized by high blood pressure and a significant amount of proteins released in the urine. Although there is a substantial amount of research on PE, the exact pathogenesis is not known. Reactive Oxygen species (ROS) are a compound produced during metabolism that play a role in cell signaling, but can have many harmful effects in high concentrations. Oxidative stress is caused by too much ROS production and not enough ROS clearing mechanisms. This study attempts to show how ROS in the RVLM are related to the cardiovascular problems associated with PE.
Ninety Sprague Dawley rats were used in this study. Desoxycorticosterone acetate (DOCA) is a hormone that causes signs of PE such as high blood pressure and high levels of proteins in urine. Pregnant rats were treated with DOCA to produce an animal model of PE. This study involved four groups of rats: a non-pregnant control group, a non-pregnant group treated with DOCA and saline (NPS), a pregnant group without any DOCA (NP), and a pregnant group treated with DOCA and saline (PDS). Vaginal smearing was used to confirm that the rats were pregnant. After about 18 days of pregnancy, 24 hour urine samples were collected. High-performance liquid chromatography and an enzyme linked immunosorbent assay were used to measure the levels of proteins in the urine samples. To detect ROS, fluorescence microtopography was used, specifically Dihydroethidium (DHE). A microinjection of Tempol, which is a catalyst that can limit ROS, was performed on the RVLM to see the effects on blood pressure, heart rate, and nerve activity. Sympathetic nerve activity was measured at the renal nerve.
The urine samples collected after 18 days of pregnancy showed that the protein concentration was significantly increased in the PDS group, compared to the control. While there was a small protein concentration level increase in the NPS and NP groups, it was not significantly different from the control. The PDS group also exhibited significant increases in blood pressure and levels of norepinephrine in the urine. The NP and PDS groups both exhibited a significant increase in heart rate when compared to the control group. Examining the results of the fluorescence microtopography showed that ROS levels in the RVLM were significantly higher in the PDS group, compared to the control. ROS levels were shown to be about seven times higher than the control. The enzyme NOX4 was also shown to be upregulated in PDS group, which is responsible for the production of ROS. The enzyme SOD1, which can limit the damaging effects of ROS, did not significantly change in any of the groups when compared to the control. The microinjection of Tempol into the RVLM demonstrated a significant decrease in blood pressure, heart rate, and renal sympathetic nerve activity in the PDS group. The NPS and NP groups did not show a significant change compared to the control.
In conclusion, DOCA was shown to increase protein levels in urine, including norepinephrine. DOCA also caused an increase in heart rate, blood pressure, and ROS. NOX4, which helps produce ROS, was shown to increase when DOCA was injected, while the ROS limiting enzyme SOD1 stayed constant. Overall, DOCA was able to produce a mouse model that exhibits PE symptoms. When treated with Tempol, this mouse model exhibited improved symptoms. Tempol is demonstrated to be a possible therapy for PE or other problems involving oxidative stress in the RVLM. In relation to what we are working on lab, I would like to further understand the role of ROS in the RVLM when comparing different lifestyles. Does a sedentary lifestyle always lead to an increase of ROS in the RVLM? If so, I’m curious what factors are causing ROS to upregulated when compared to a more active individual.
-Paul
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