Key result
Pressive doses of Angiotensin II significantly increased hippocampal inflammation and altered microglial morphology in mice, effects that were prevented by lowering blood pressure with hydralazine.
Why the study?
Does Angiotensin II and blood pressure differentially contribute to hippocampal inflammation in mice?
Does Angiotensin II and blood pressure differentially contribute to hippocampal inflammation in mice?
Both increased blood pressure and Angiotensin II contribute to hippocampal inflammation in mice, suggesting that controlling blood pressure may reduce brain inflammation associated with hypertension.
Does not support changing hypertension management; leaves open Ang II versus BP effects on hippocampal inflammation in humans.
BACKGROUND: Angiotensin II (Ang II), a peptide hormone involved in the development of hypertension, causes systemic and cerebral inflammation, affecting brain regions important for blood pressure control. The cause-and-effect relationship between hypertension and inflammation is two-way, but the role of blood pressure in the induction of cerebral inflammation is less clear. The vulnerability of specific brain regions, particularly those important for memory, is also of interest. METHODS: We used molecular biology approaches, immunohistochemistry, and electron microscopy to examine the interdependence between the hypertensive and pro-inflammatory effects of Ang II. We examined the effect of blood pressure by administering a subpressive (200 ng/kg/min) or a pressive Ang II dose (1000 or 1900 ng/kg/min) with and without hydralazine (150 mg/L) for 1 week and used phenylephrine to increase blood pressure independently of the renin-angiotensin system. RESULTS: Ang II increased ionized calcium-binding adaptor molecule 1 (Iba-1) levels (marker of microgliosis) in the whole brain and in the hippocampus in a dose-dependent manner. Pressive Ang II induced specific changes in microglial morphology, indicating differences in functional phenotype. An increase in hippocampal glial fibrillary acidic protein (GFAP) was seen in mice receiving pressive Ang II, while no induction of cerebral gliosis was observed after 7 days of subpressive Ang II infusion. Although phenylephrine led to increased astrogliosis, it did not affect Iba-1 expression. Pressive Ang II stimulated TNF-α production in the hippocampus, and daily treatment with hydralazine prevented this increase. Hydralazine also reduced GFAP and Iba-1 levels. With longer perfusion (14 days), subpressive Ang II led to some but not all the inflammatory changes detected with the pressive doses, mainly an increase in CD68 and Iba-1 but not of GFAP or TNF-α. CONCLUSIONS: Blood pressure and Ang II differentially contribute to hippocampal inflammation in mice. Control of blood pressure and Ang II levels should prevent or reduce brain inflammation and therefore brain dysfunctions associated with hypertension.
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Iulita et al. (2018) studied Hypertension and cerebral inflammation. Angiotensin II vs. Saline (0.9%) was evaluated on Hippocampal inflammation (Iba-1, GFAP, and TNF-α levels). Pressive doses of Angiotensin II significantly increased hippocampal inflammation and altered microglial morphology in mice, effects that were prevented by lowering blood pressure with hydralazine.
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