Abstract 13856: Autoimplantation of Astrocytes into Cardiovascular Center of Brainstem Causes Sympathoinhibition and Decreases the Mortality Rate in Hypertensive Rats
Backgrounds: Long considered merely a mechanical support to neurons, astrocytes have been shown to protect and mediate neural function. In hypertensive model rats with sympathoexcitation, we previously demonstrated that astrocytes were decreased in the rostral ventrolateral medulla (RVLM), known as a cardiovascular center. However, the role of astrocytes in the RVLM in regulating the sympathetic nerve activity (SNA) remains unknown. We hypothesized that astrocytes in the RVLM inhibits SNA. To test our hypothesis, we examined whether an autoimplantation of astrocytes into the RVLM inhibits SNA and improves the mortality rate of hypertensive rats.
Methods and Results: We used 8 weeks old stroke-prone spontaneously hypertensive rats (SHRSP) as hypertensive model with sympathoexcitation. From the tissue of lateral ventricle, neural stem cells were isolated by a cell sphere method. Neural stem cells cocultured with leukocyte inhibitory factor and bone morphogenetic protein receptor 2 induced the differentiation for astrocytes. We divided salt-loaded SHRSPs into two groups, the astrocyte-autoimplanted SHRSP (SHRSP-astrocyte) group and the SHRSP-control group. Astrocytes were microinjected into bilateral RVLM of SHRSP-astrocyte group. Telemetrically measured mean arterial pressure (MAP) and urinary norepinephrine excretion (uNE), a parameter of SNA, were significantly lower in the SHRSP-astrocyte group at 14 days after autoimplantation than in the SHRSP-astrocyte group at pre-autoimplantation (MAP; 104±9 mmHg vs. 156±14 mmHg, uNE; 1.1±0.2 μg vs. 1.9±0.3 μg, n=5 for each, P<0.01 for each). Furthermore, at 14 days after the autoimplantation, MAP and uNE were also significantly lower in the SHRSP-astrocyte group than in the SHRSP-control. These inhibitions of MBP and SNA were continued until 22 weeks old. The mortality rate at 22 weeks old was significantly lower in the SHRSP-astrocyte group than in the SHRSP-control group (8% vs. 76%, P<0.01).
Conclusions: Autoimplantation of astrocytes into the RVLM of SHRSP causes sympathoinhibition and decreases the mortality rate for a long period. These results suggest that the apoptosis of astrocyte in the RVLM plays a major role in the pathogenesis of hypertension with excessive sympathoexcitation.
- © 2010 by American Heart Association, Inc.