Abstract 13861: Apoptosis of Astrocyte Mediated by Toll-like Receptor 4 in the Cardiovascular Center Causes Excessive Sympathoexcitation in Hypertensive Rats
Backgrounds: Long considered merely a mechanical support to neurons, astrocytes have been shown to protect and mediate neural function. We previously demonstrated that oxidative stress-induced apoptosis in the rostral ventrolateral medulla (RVLM) of brainstem contributes to sympathoexcitation in hypertension. However, which cell becomes apoptotic, neurons or astrocytes, remains unknown. Toll-like receptor 4 (TLR4), known to regulate inflammatory reactions mainly, is activated by oxidative stress and causes neural apoptosis. We hypothesized that TLR4-induced apoptosis of astrocytes in the RVLM results in sympathoexcitation in hypertension.
Methods and Results: We used 16–18 weeks old stroke-prone spontaneously hypertensive rats (SHRSP) as a hypertensive model with increased sympathetic nerve activity (SNA) and Wister-Kyoto rats (WKY) as control. Immunohistochemical staining revealed that the number of astrocyte per total cell counts in the RVLM was significantly lower in SHRSP than in WKY (29±5 % vs. 48±4 %, n=5, P<0.05). The expression of TLR4 in the RVLM was significantly higher in SHRSP than in WKY (23±2 %, n=5, P<0.01). Telemetrically measured mean blood pressure was significantly lower in TLR4 antagonist-infused SHRSP (intracerebroventricularly, for 14 days) than in vehicle-infused SHRSP (112±13 mmHg vs 152±13 mmHg, n=5 for each, P<0.01). Urinary norepinephrine excretion (uNE), a parameter of SNA, was significantly higher in SHRSP than in WKY, and was significantly lower in TLR4 antagonist-infused SHRSP than in vehicle-infused SHRSP (1.3±0.2 μg vs 1.8±0.2 μg, n=5 for each, P<0.01). Moreover, the number of astrocyte per total cell counts in the RVLM was significantly higher in TLR4 antagonist-infused SHRSP than in vehicle-infused SHRSP (56±8 % vs 33±4 %, n=5 for each, P<0.01).
Conclusions: TLR4-induced apoptosis of astrocyte in the RVLM plays a key role for sympathoexcitation in hypertensive rats.
- © 2010 by American Heart Association, Inc.