Description:
Accumulating evidence supports microglia‐mediated inflammatory pathways within the brain to contribute to cardiovascular disorders including hypertension. Yet, the precise mechanisms remain unknown. Here, we start to test the hypothesis of a pathophysiological link between angiotensin II (AngII) and microglial cells in the hypothalamic paraventricular nucleus (PVN) of hypertensive rats, via activation of toll like receptor 4 (TLR4). In a first series of immunohistochemical experiments, we found a significant increase in microglia (IBA1) as well as TLR4 immunoreactivity in SHR compared to WKY rats (71% and 106%). Importantly, a high degree of colocalization between both markers was observed in SHRs. In vitro experiments performed in acute hypothalamic slices showed that exposure of slices to AngII (1μM) significantly increased the density of activated microglial cells in the PVN of WKY rats (64%). Compared to WKYs, basal microglial cell density was significantly higher in SHRs (45%), in which AngII failed to further increase microglial staining. Ongoing experiments are being performed in C3H/HeJ mutant mice to determine the contribution of TLR4 to AngII‐mediated microglial activation in the PVN. Taken together, our results support the notion that AngII contributes to microglial cell activation in the PVN of SHRs, likely via activation and/or upregulation TLR4 receptors. Supported by RO1 HL 090948.