Abstract 208: Action of Multifaceted Microglia on Blood Pressure Control
Microglia are the resident surveillance cells in the CNS, and are involved in shaping neuronal plasticity. Previous studies show that hypertension is associated with neuroinflammation. Interference of neuroinflammation by targeting microglia can inhibit or attenuate hypertension. To investigate the phenotypic changes of microglia during hypertension, we compared the profiles of microglia dissociated from normotensive and Ang II-induced hypertensive mice by flow cytometry. We found significant increases in the expression of CD89 (76%), CCR7 (52%), IFNγR (150%), MHC II (85%), CCR2 (51%), IL-4R (164%), mannose receptor (61%) and CD36 (60%) in Ang II microglia compared to the controls. To understand whether the microglial activation has a direct effect on blood pressure, we utilized microglia adoptive transfer strategy via intracerebroventricular (ICV) injection and then examined the blood pressure responses. Mouse microglial cell line, N9, was stimulated in groups as follows: 1) medium control, 2) 10 ng/ml LPS, 3)10 ng/ml LPS + 100 μM minocycline. After 6 hr treatment, half a million N9 cells were transferred into mice via ICV injection. Twenty-four hr later, the recipient mice were anesthetized, cannulated and positioned on the stereotaxic frame. The baseline blood pressure and heart rates were similar among groups (82±2 mmHg, 328±12.8 bpm). However, when we injected Ang II (50 ng in 1μl, ICV), there was a significant prolonged response in the recipient mice transferred with LPS-primed microglia compared to the ones receiving naïve controls (LPS 817±170 sec vs. control 475±70 sec; P<0.05 by unpaired T-test). This increase was fully abolished by co-incubation with minocycline, an inhibitor for microglial activation (LPS+minocycline 507±33 sec). There were no differences observed in pressure magnitude to ICV Ang II across the groups (11±2 mmHg). These data suggest that activated microglia alter neuronal plasticity and potentiate the neuronal responses to Ang II challenge. Taken together, microglial cells are activated, manifested by up-regulation of myeloid cell differentiation markers during hypertension, and then participate in the modulation of blood pressure.
Author Disclosures: Y. Li: None. L. Li: None. Z. Shan: None. K.E. Bernstein: None. X. Shen: None. P. Shi: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Significant; AHA SDG 11SDG6770006; CTSI UL1TR000124.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2014 by American Heart Association, Inc.